{
    "componentChunkName": "component---src-gatsby-pdf-topic-pdf-tsx",
    "path": "/pdf/topics/cell-and-gene-engineering",
    "result": {"data":{"platform":{"topic":{"id":"65c55d599e947c438698b7b7","slug":"cell-and-gene-engineering","name":"Cell and Gene Engineering","path":"/topics/cell-and-gene-engineering","__typename":"Platform_Topic","created":"2021-07-26T04:51:40.00","published":null,"doiId":null,"outlineNumber":"2.2","trend":{"id":"65c55d5c9e947c438698b86b","path":"/trends/human-augmentation","slug":"human-augmentation","name":"Human Augmentation","__typename":"Platform_Trend","outlineNumber":"2","openGraph":{"image":{"thumbnails":{"card":{"url":"https://res.cloudinary.com/shapeable/image/upload/c_limit,w_480/v1760333268/gesda-platform/banner/banner-trend-2_image__P2A_2026_trhfij.webp"}}}},"color":{"id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"}},"description":{"text":"The ultimate goal for gene editing is a one-shot wonder drug — a one-time injection that cures heritable or acquired disease for the rest of the patient’s life. However, it is becoming increasingly clear that the gene-editing tool that has underpinned most clinical and research breakthroughs will not be the main way forward. CRISPR, an editor that can snip DNA to alter its sequence, also creates dangerous and irreversible breaks in DNA.[6](/citation/2025-02-2-2-6/) The future of gene editing will rely on new, more efficient, more accurate techniques now under investigation and in early trials, along with novel ideas about how to manipulate the genome indirectly, transiently and even perhaps reversibly. \n\nThey will also rely on improved delivery methods. Today, most gene editing is not applied to living embryos or directly done on patients, but is ex vivo: as, for example, in treatments for sickle-cell anaemia.[7](/citation/2025-02-2-2-7/) But this limits the number of diseases that can be targeted. Targeted payload delivery is being developed to be more precise and less toxic, thereby creating fewer side effects and immune reactions. This could deliver the editor into tissues that are traditionally hard to reach. Better diagnostics, editors and delivery methods could be a result of advances in machine learning. AI could make it easier to diagnose and even predict heritable disorders.\n\nIt is generally agreed that future research needs to move forward with an eye to lowering the staggering costs of gene therapy. Currently, the biggest barriers to making gene editing a medical reality are not only technological: they also include public-health messaging, infrastructure and cost. Recently approved haemophilia and sickle-cell disease therapies cost $2 million to $3 million.[8](/citation/2025-02-2-2-8/) The expense is multifactorial, but new initiatives are under way to make them cheaper and more accessible.[9](/citation/2025-02-2-2-9/) Crucial to the future of scientific success will be public acceptance and understanding that this is not always led by the West.[10](/citation/2025-02-2-2-10/) As this therapeutic modality moves into more medical interventions, more infrastructure needs to be developed to address the interpretability of the science (for example, genetic counsellors are needed to interpret genetic test results but are in short supply).\n\n\n**KEY TAKEAWAYS**\n\nEditing human genetics is a promising route towards disease prevention and reduction. Work to improve **Diagnostics** tools for reading and interpreting the genome has achieved fast identification of pathogens and promises to enable insight into the most suitable gene therapies for an individual. This will be complemented by developments in **Next-generation editors and delivery**, which will manipulate the genome in ways that avoid unwanted immune-system responses. A number of processes will benefit from **Engineered organisms and AI-based tools**, such as testing of proposed therapies on synthetic organisms and accelerated reading of whole genomes through the use of AI. Researchers are exploring **Alternatives to direct gene editing**, including epigenome editing, which might facilitate the fine-grained control of gene expression."},"intro":{"text":"Gene editing has achieved significant successes in a range of areas and has gained regulatory approval for targeting cancer, [1](/citation/2025-02-2-2-1/),[2](/citation/2025-02-2-2-2/),[3](/citation/2025-02-2-2-3/) eye diseases[4](/citation/2025-02-2-2-4/) and blood diseases.[5](/citation/2025-02-2-2-5/) Its next act will be to move from rare and difficult diseases into more common disorders and cancers, and from there into cracking the fundamentals of ageing."},"anticipatoryImpact":{"text":"Three fundamental questions guide GESDA’s mission and drive its work: Who are we, as humans? How can we all live together? How can we ensure the well-being of humankind and the sustainable future of our planet? We asked researchers from the field to anticipate what impact future breakthroughs could have on each of these dimensions. This wheel summarises their opinions when considering each of these questions, with a higher score indicating high anticipated impact, and vice versa.\n\n* Anticipated impact on who we are as humans\n* Anticipated impact on how we will all live together\n* Anticipated impact on the well-being of humankind and sustainable future of our planet"},"indicatorValues":[{"id":"65c55cf49e947c438698aa9b","value":"0.490","numericValue":0.49,"year":2024,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}},{"id":"68a686290ac1330579fd789b","value":"0.5818","numericValue":0.5818,"year":2025,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}}],"editions":[{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024","numericValue":2024},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025","numericValue":2025}],"anticipatoryImpactImage":{"image":{"id":"image_gesda-platform/image-asset/psp-pl-2-25-2-2_image__PSP-PL2_25_2.2_rpctpc","url":"https://res.cloudinary.com/shapeable/image/upload/v1760070017/gesda-platform/image-asset/psp-pl-2-25-2-2_image__PSP-PL2_25_2.2_rpctpc.webp"}},"embeds":{"citations":[{"id":"691a788dc0043bba84a9de93","slug":"2025-02-2-2-1","url":"https://www.cancer.gov/news-events/cancer-currents-blog/2024/fda-amtagvi-til-therapy-melanoma","name":"First Cancer TIL Therapy Gets FDA Approval for Advanced Melanoma","authors":[{"id":"691a788dc0043bba84a9de91","name":"National Cancer Institute","slug":"national-cancer-institute"}],"authorShowsEtAl":null,"edition":null,"publication":"cancer.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":1,"year":null},{"id":"691a788ec0043bba84a9de95","slug":"2025-02-2-2-2","url":"https://www.science.org/content/article/cutting-edge-crispr-gene-editing-appears-safe-three-cancer-patients","name":"Cutting-Edge CRISPR Gene Editing Appears Safe in Three Cancer Patients","authors":[{"id":"65c55c9b9e947c4386989a43","name":"J. Couzin-Frankel","slug":"j-couzin-frankel"}],"authorShowsEtAl":null,"edition":null,"publication":"Science","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":2,"year":null},{"id":"691a788ec0043bba84a9de97","slug":"2025-02-2-2-3","url":"https://www.npr.org/sections/health-shots/2022/12/13/1140384354/crispr-improves-cancer-immunotherapy-car-t-cell","name":"CRISPR Gene-Editing May Boost Cancer Immunotherapy () New Study Finds","authors":[{"id":"65c55c9b9e947c4386989bd3","name":"R. Stein","slug":"r-stein"}],"authorShowsEtAl":null,"edition":null,"publication":"NPR","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":3,"year":null},{"id":"691a788ec0043bba84a9de99","slug":"2025-02-2-2-4","url":"https://www.ema.europa.eu/en/news/new-gene-therapy-rare-inherited-disorder-causing-vision-loss-recommended-approval","name":"New gene therapy for rare inherited disorder causing vision loss recommended for approval","authors":[{"id":"66f4d37c09a10d3d0e148ca4","name":"EMA","slug":"ema"}],"authorShowsEtAl":null,"edition":null,"publication":"europa.eu","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":4,"year":null},{"id":"691a788fc0043bba84a9de9d","slug":"2025-02-2-2-5","url":"https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease","name":"FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease","authors":[{"id":"691a788ec0043bba84a9de9b","name":"US Food and Drug Administration","slug":"us-food-and-drug-administration"}],"authorShowsEtAl":null,"edition":null,"publication":"fda.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":5,"year":null},{"id":"691a788fc0043bba84a9dea1","slug":"2025-02-2-2-6","url":"https://doi.org/10.1126/sciadv.adk8052","name":"Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3","authors":[{"id":"691a788fc0043bba84a9de9f","name":"J. Li et al","slug":"j-li-et-al"}],"authorShowsEtAl":null,"edition":null,"publication":"Science Advances","accessDate":null,"startPage":8052,"volume":10,"footnoteNumber":6,"year":null},{"id":"691a7890c0043bba84a9dea5","slug":"2025-02-2-2-7","url":"https://clinicaltrials.gov/ct2/show/NCT03745287","name":"A Phase 1/2/3 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease","authors":[{"id":"691a7890c0043bba84a9dea3","name":"Vertex Pharmaceuticals Incorporated","slug":"vertex-pharmaceuticals-incorporated"}],"authorShowsEtAl":null,"edition":null,"publication":"clinicaltrials.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":7,"year":null},{"id":"691a7890c0043bba84a9dea7","slug":"2025-02-2-2-8","url":"https://www.managedhealthcareexecutive.com/view/gene-therapy-for-hemophilia-is-becoming-a-reality-who-will-write-the-check-to-pay-for-it-","name":"Gene Therapy for Hemophilia Is Becoming a Reality. Who Will Write the Checks to Pay for It?","authors":[{"id":"66f4d37d09a10d3d0e148cb2","name":"T. Hagen","slug":"t-hagen"}],"authorShowsEtAl":null,"edition":null,"publication":"Managed Healthcare Executive","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":8,"year":null},{"id":"691a7890c0043bba84a9dea9","slug":"2025-02-2-2-9","url":"https://www.bizjournals.com/bizwomen/news/profiles-strategies/2023/07/uc-berkeley-jennifer-doudna-cell-gene-therapy-igi.html","name":"Task force from Nobel-winner Jennifer Doudna's institute points way to cheaper, more accessible gene therapies","authors":[{"id":"66f4d37e09a10d3d0e148cb6","name":"R. Leuty","slug":"r-leuty"}],"authorShowsEtAl":null,"edition":null,"publication":"The Business Journals","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":9,"year":null},{"id":"691a7891c0043bba84a9dead","slug":"2025-02-2-2-10","url":"httos://doi.org/10.1007/s12687-023-00689-1","name":"Survey of attitude to human genome modification in Nigeria","authors":[{"id":"691a7891c0043bba84a9deab","name":"M. Jibrilla M et al.","slug":"m-jibrilla-m-et-al"}],"authorShowsEtAl":null,"edition":null,"publication":"Journal of Community Genetics","accessDate":null,"startPage":1,"volume":15,"footnoteNumber":10,"year":null}],"imageAssets":[]},"surveyObservations":{"text":"The relatively low Anticipation Potential scores for the sub-topics covered in the Cell and Gene Engineering topic are linked to lower transformative effects scores and the high awareness they benefit from. The ability to use AI to engineer new organisms is still in its early phase and will require more than 10 years of further research before transformative effects on society and the economy start to be seen. Combined with the high uncertainty, this explains the higher Anticipation Potential score for this field."},"color":{"id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD","darkValue":"#045059","veryDarkValue":"#011b1e"},"banner":{"id":"6a923fed9d83c3b6c148540f","name":"\"The inner workings of a dividing cell\" by Joana Delgado Martins, University of Zurich","description":{"text":"\"The inner workings of a dividing cell\" by Joana Delgado Martins, University of Zurich"},"image":{"id":"image_gesda-platform/banner/the-inner-workings-of-a-dividing-cell-by-joana-delgado-martins-university-of-zurich_image__22The_inner_workings_of_a_dividing_cell_22_by_Joana_Delgado_Martins_University_of_Zurich_tttmyp","url":"https://res.cloudinary.com/shapeable/image/upload/v1787969507/gesda-platform/banner/the-inner-workings-of-a-dividing-cell-by-joana-delgado-martins-university-of-zurich_image__22The_inner_workings_of_a_dividing_cell_22_by_Joana_Delgado_Martins_University_of_Zurich_tttmyp.jpg","thumbnails":{"mainBanner":{"url":"https://res.cloudinary.com/shapeable/image/upload/c_limit,w_1440/v1787969507/gesda-platform/banner/the-inner-workings-of-a-dividing-cell-by-joana-delgado-martins-university-of-zurich_image__22The_inner_workings_of_a_dividing_cell_22_by_Joana_Delgado_Martins_University_of_Zurich_tttmyp.jpg","url2x":"https://res.cloudinary.com/shapeable/image/upload/c_limit,w_2880/v1787969507/gesda-platform/banner/the-inner-workings-of-a-dividing-cell-by-joana-delgado-martins-university-of-zurich_image__22The_inner_workings_of_a_dividing_cell_22_by_Joana_Delgado_Martins_University_of_Zurich_tttmyp.jpg"}}}},"chartImage":{"id":"65c55cee9e947c438698a95f","slug":"chart-2-2-human-applications-of-genetic-engineering","image":{"id":"image_gesda-22/image-asset/chart-2-2-human-applications-of-genetic-engineering_image__TRR-2_2-TBC-01","url":"https://res.cloudinary.com/shapeable/image/upload/v1668986374/gesda-22/image-asset/chart-2-2-human-applications-of-genetic-engineering_image__TRR-2_2-TBC-01.png","url2x":null}},"citations":[{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-1","url":"https://www.cancer.gov/news-events/cancer-currents-blog/2024/fda-amtagvi-til-therapy-melanoma","name":"First Cancer TIL Therapy Gets FDA Approval for Advanced Melanoma","authors":[{"id":"691a788dc0043bba84a9de91","name":"National Cancer Institute","slug":"national-cancer-institute"}],"authorShowsEtAl":null,"edition":null,"publication":"cancer.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":1,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-2","url":"https://www.science.org/content/article/cutting-edge-crispr-gene-editing-appears-safe-three-cancer-patients","name":"Cutting-Edge CRISPR Gene Editing Appears Safe in Three Cancer Patients","authors":[{"id":"65c55c9b9e947c4386989a43","name":"J. Couzin-Frankel","slug":"j-couzin-frankel"}],"authorShowsEtAl":null,"edition":null,"publication":"Science","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":2,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-3","url":"https://www.npr.org/sections/health-shots/2022/12/13/1140384354/crispr-improves-cancer-immunotherapy-car-t-cell","name":"CRISPR Gene-Editing May Boost Cancer Immunotherapy () New Study Finds","authors":[{"id":"65c55c9b9e947c4386989bd3","name":"R. Stein","slug":"r-stein"}],"authorShowsEtAl":null,"edition":null,"publication":"NPR","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":3,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-4","url":"https://www.ema.europa.eu/en/news/new-gene-therapy-rare-inherited-disorder-causing-vision-loss-recommended-approval","name":"New gene therapy for rare inherited disorder causing vision loss recommended for approval","authors":[{"id":"66f4d37c09a10d3d0e148ca4","name":"EMA","slug":"ema"}],"authorShowsEtAl":null,"edition":null,"publication":"europa.eu","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":4,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-5","url":"https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease","name":"FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease","authors":[{"id":"691a788ec0043bba84a9de9b","name":"US Food and Drug Administration","slug":"us-food-and-drug-administration"}],"authorShowsEtAl":null,"edition":null,"publication":"fda.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":5,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Journal","slug":"2025-02-2-2-6","url":"https://doi.org/10.1126/sciadv.adk8052","name":"Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3","authors":[{"id":"691a788fc0043bba84a9de9f","name":"J. Li et al","slug":"j-li-et-al"}],"authorShowsEtAl":null,"edition":null,"publication":"Science Advances","accessDate":null,"startPage":8052,"volume":10,"footnoteNumber":6,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Web page","slug":"2025-02-2-2-7","url":"https://clinicaltrials.gov/ct2/show/NCT03745287","name":"A Phase 1/2/3 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease","authors":[{"id":"691a7890c0043bba84a9dea3","name":"Vertex Pharmaceuticals Incorporated","slug":"vertex-pharmaceuticals-incorporated"}],"authorShowsEtAl":null,"edition":null,"publication":"clinicaltrials.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":7,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Report","slug":"2025-02-2-2-8","url":"https://www.managedhealthcareexecutive.com/view/gene-therapy-for-hemophilia-is-becoming-a-reality-who-will-write-the-check-to-pay-for-it-","name":"Gene Therapy for Hemophilia Is Becoming a Reality. Who Will Write the Checks to Pay for It?","authors":[{"id":"66f4d37d09a10d3d0e148cb2","name":"T. Hagen","slug":"t-hagen"}],"authorShowsEtAl":null,"edition":null,"publication":"Managed Healthcare Executive","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":8,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Journal","slug":"2025-02-2-2-9","url":"https://www.bizjournals.com/bizwomen/news/profiles-strategies/2023/07/uc-berkeley-jennifer-doudna-cell-gene-therapy-igi.html","name":"Task force from Nobel-winner Jennifer Doudna's institute points way to cheaper, more accessible gene therapies","authors":[{"id":"66f4d37e09a10d3d0e148cb6","name":"R. Leuty","slug":"r-leuty"}],"authorShowsEtAl":null,"edition":null,"publication":"The Business Journals","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":9,"year":null},{"__typename":"Platform_Citation","_schema":{"label":"Citation","pluralLabel":"Citations"},"typeLabel":"Journal","slug":"2025-02-2-2-10","url":"httos://doi.org/10.1007/s12687-023-00689-1","name":"Survey of attitude to human genome modification in Nigeria","authors":[{"id":"691a7891c0043bba84a9deab","name":"M. Jibrilla M et al.","slug":"m-jibrilla-m-et-al"}],"authorShowsEtAl":null,"edition":null,"publication":"Journal of Community Genetics","accessDate":null,"startPage":1,"volume":15,"footnoteNumber":10,"year":null}],"subTopics":[{"id":"65c55d4f9e947c438698b667","name":"Diagnostics","path":"/sub-topics/diagnostics","outlineNumber":"2.2.1","slug":"diagnostics","__typename":"Platform_SubTopic","color":{"id":"65c55cbc9e947c438698a325","name":"Teal","value":"#44AFCD"},"topic":{"id":"65c55d599e947c438698b7b7","slug":"cell-and-gene-engineering","path":"/topics/cell-and-gene-engineering"},"intro":{"text":"Reading and interpreting the genome — whole-genome sequencing of patient DNA — is increasingly common in medical practice for developing and adequately deploying therapeutics. Better reading technologies have already helped to diagnose disease, genetic predispositions to disease and even infections.[11](/citation/2025-02-2-2-11/) For example, the CRISPR-Cas system is enabling the fast detection of pathogens: Cas12a has detected hepatitis B in less than 30 minutes.[12](/citation/2025-02-2-2-12/) More typically, sequencing is now possible in hours to days.[13](/citation/2025-02-2-2-13/) Costs are also falling.[14](/citation/2025-02-2-2-14/)"},"description":{"text":"Faster, better and cheaper diagnostics coming into the mainstream will act as a fact-checker on the new generations of genome editors, detecting and preventing DNA-editing errors. These technologies need to be further refined to ensure every laboratory can easily adopt them when in vivo editing becomes mainstream.\n\nMuch progress will be thanks to the new ability to do long-read sequencing, more accurate than the previously more common usage of short-read sequencing. This could identify more clinically relevant gene variants and it could also provide epigenetic information that can bring epigenome editing to the clinic.[15](/citation/2025-02-2-2-15/) Diagnostics will be able to tell patients what kind of gene therapy they are suited for, or even which interventions and lifestyle changes will most affect their chances of expressing a genetic disease. However, analysis and interpretation are a major bottleneck: a shortage of genetic counsellors is an increasing problem.[16](/citation/2025-02-2-2-16/)"},"anticipationScores":{"text":"The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate: \n\n1. The *uncertainty* related to future science breakthroughs in the field\n2. The *transformative* *effect* anticipated breakthroughs may have on research and society\n3. The *scope for action* in the present in relation to anticipated breakthroughs. \n\nThis chart represents a summary of their responses to each of these elements, which when combined, provide the *Anticipation Potential* for the topic. See [methodology](/science-anticipation/methodology) for more information."},"anticipationScoresImage":{"id":"68e8a28663d1c853e9788cd8","image":{"id":"image_gesda-platform/image-asset/2-2-1-sub-anti-2026_image__2.2.1_sub_anti_2026_xu4xve","url":"https://res.cloudinary.com/shapeable/image/upload/v1760076407/gesda-platform/image-asset/2-2-1-sub-anti-2026_image__2.2.1_sub_anti_2026_xu4xve.webp","url2x":null,"width":1200,"height":1200}},"horizons":[{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a793","name":"2.2.1 - 25-year horizon","slug":"2-2-1-25-year-horizon","intro":{"text":"Gene-reading goes mainstream"},"description":{"text":"Rapid diagnostics enable to-go or home-based devices for pathogen detection and better prediction of complex diseases. Editing technology, combined with AI, obviates most genetic concerns over partner choice. Heritability and environmental conditions are included in assessments of polygenic risk scores for everything from cancer to obesity."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89c","name":"25-year horizon","slug":"25-year-horizon","years":25,"title":"25-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a792","name":"2.2.1 - 10-year horizon","slug":"2-2-1-10-year-horizon","intro":{"text":"Genome-reading finds a broad range of applications"},"description":{"text":"The time for whole-human-genome sequencing drops to an hour. Same-day diagnosis of cancers and rare diseases shortens time to treatment. Genome sequencing influences retirement plans and insurance. AI helps fill unmet need for genetic counsellors."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89b","name":"10-year horizon","slug":"10-year-horizon","years":10,"title":"10-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a791","name":"2.2.1 - 5-year horizon","slug":"2-2-1-5-year-horizon","intro":{"text":"Faster, cheaper, better diagnostics become available"},"description":{"text":"CRISPR-based diagnostic methods are developed for a variety of targets, including cancer, viruses and other pathogens. Rapid, reliable, widespread whole-genome sequencing shortens rare-disease diagnosis and cancer diagnosis, prognosis and management. Cost drops to $100 to $200 a genome.[17](/citation/2025-02-2-2-17/) Therapeutic investment explodes. Genome targeting for pathogen diagnosis comes to point-of-care settings, including pharmacogenomics when drugs are prescribed. AI interprets sequencing."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89a","name":"5-year horizon","slug":"5-year-horizon","years":5,"title":"5-year","subtitle":"horizon"},"embeds":{"citations":[{"slug":"2025-02-2-2-17","url":"https://www.statnews.com/2023/03/22/euan-ashley-stanford-genome-sequencing/","name":"Stanford Scientist Who Broke Genome Sequencing Record on What Faster Diagnoses Mean for Patients","authors":[{"id":"65c55c9b9e947c4386989a70","name":"J. Wosen"}],"authorShowsEtAl":null,"edition":null,"publication":"STAT","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":17,"year":null}]}}],"indicatorValues":[{"id":"65c55cf49e947c438698aa99","value":"0.506","numericValue":0.506,"year":2024,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}},{"id":"68edd9faaf9e6d6d63270dac","value":"0.540","numericValue":0.54,"year":2025,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}}],"embeds":{"citations":[{"slug":"2025-02-2-2-11","url":"https://doi.org/10.1503/cmaj.210549","name":"Genome Sequencing as a Diagnostic Test","authors":[{"name":"G. Costain et al."}],"authorShowsEtAl":null,"edition":null,"publication":"CMAJ","accessDate":null,"startPage":1626,"volume":193,"footnoteNumber":11,"year":null},{"slug":"2025-02-2-2-12","url":"https://doi.org/10.3390/ijms22094842","name":"CRISPR/Cas12-Based Ultra-Sensitive and Specific Point-of-Care Detection of HBV","authors":[{"name":"R. Ding et al."}],"authorShowsEtAl":null,"edition":null,"publication":"International Journal of Molecular Sciences","accessDate":null,"startPage":4842,"volume":22,"footnoteNumber":12,"year":null},{"slug":"2025-02-2-2-13","url":"https://www.nature.com/articles/d41586-024-00483-0","name":"Streamlined workflows for DNA and RNA sequencing are helping clinicians to deliver prompt, targeted care to people in days — or even hours","authors":[{"name":"M. Eisenstein"}],"authorShowsEtAl":null,"edition":null,"publication":"Nature","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":13,"year":null},{"slug":"2025-02-2-2-14","url":"https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost","name":"The Cost of Sequencing a Human Genome","authors":[{"name":"National Human Genome Research Institute"}],"authorShowsEtAl":null,"edition":null,"publication":"Genome.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":14,"year":null},{"slug":"2025-02-2-2-15","url":"https://doi.org/10.1038/s41592-022-01730-w","name":"Method of the year: long-read sequencing","authors":[{"name":"V. Marx"}],"authorShowsEtAl":null,"edition":null,"publication":"Nat Methods","accessDate":null,"startPage":6,"volume":20,"footnoteNumber":15,"year":null},{"slug":"2025-02-2-2-16","url":"https://doi.org/10.1016/j.ejmg.2023.104710","name":"An European overview of genetic counselling supervision provision","authors":[{"name":"M. Paneque et al"}],"authorShowsEtAl":null,"edition":null,"publication":"European Journal of Medical Genetics","accessDate":null,"startPage":104710,"volume":66,"footnoteNumber":16,"year":null}],"imageAssets":[]}},{"id":"65c55d4f9e947c438698b68e","name":"Next-generation editors and delivery","path":"/sub-topics/next-generation-editors-and-delivery","outlineNumber":"2.2.2","slug":"next-generation-editors-and-delivery","__typename":"Platform_SubTopic","color":{"id":"65c55cbc9e947c438698a325","name":"Teal","value":"#44AFCD"},"topic":{"id":"65c55d599e947c438698b7b7","slug":"cell-and-gene-engineering","path":"/topics/cell-and-gene-engineering"},"intro":{"text":"CRISPR-Cas9 is now the most widely used gene-editing technology in the world, successfully treating blood diseases, cancers and eye diseases.[18](/citation/2025-02-2-2-18/) Several therapies have been approved for clinical use and many more are in trials. However, CRISPR’s ability to correct gene defects depends on making double-strand breaks that are repaired by cellular processes. It is increasingly accepted that such double-strand breaks are dangerous,[19](/citation/2025-02-2-2-19/) resulting in potential chromosomal rearrangements or loss.[20](/citation/2025-02-2-2-20/) Drugs in the pipeline will not be abandoned, but future therapies will rely on more efficient and accurate techniques."},"description":{"text":"The two likeliest candidates are base and prime editing. Base editing is powerful against point mutations, which account for 80 per cent of human genetic diseases.[21](/citation/2025-02-2-2-21/) It also enables mitochondrial gene editing, which is harder to achieve with CRISPR.[22](/citation/2025-02-2-2-22/) Prime editing is also more specific and accurate, and new research continues to enhance its efficiency.[23](/citation/2025-02-2-2-23/) Research is under way to replicate CRISPR successes in sickle-cell disease and beyond with base and prime editing.[24](/citation/2025-02-2-2-24/),[25](/citation/2025-02-2-2-25/),[26](/citation/2025-02-2-2-26/) Prime editing can target multiple genes at the same time.[27](/citation/2025-02-2-2-27/),[28](/citation/2025-02-2-2-28/)\n\nModified adeno-associated viruses (AAVs) can deliver gene editors, although the large quantities required can trigger dangerous immune responses. Efforts are under way to re-engineer AAV to be bigger and evade immune response. One alternative is more efficient lentiviral vectors, or viruses engineered to make them preferentially infect specific cell types, for example neural cells or airway cells.[29](/citation/2025-02-2-2-29/) \n\nNon-viral delivery has become an increasingly viable alternative, thanks to rapid progress in the use of lipid nanoparticles and inorganic nanoparticle-based delivery systems.[30](/citation/2025-02-2-2-30/),[31](/citation/2025-02-2-2-31/)"},"anticipationScores":{"text":"The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate: \n\n1. The *uncertainty* related to future science breakthroughs in the field\n2. The *transformative* *effect* anticipated breakthroughs may have on research and society\n3. The *scope for action* in the present in relation to anticipated breakthroughs. \n\nThis chart represents a summary of their responses to each of these elements, which when combined, provide the *Anticipation Potential* for the topic. See [methodology](/science-anticipation/methodology) for more information."},"anticipationScoresImage":{"id":"68e89a0063d1c853e9788c2a","image":{"id":"image_gesda-platform/image-asset/2-2-2-sub-anti-2026_image__2.2.2_sub_anti_2026_gh6oxy","url":"https://res.cloudinary.com/shapeable/image/upload/v1760074221/gesda-platform/image-asset/2-2-2-sub-anti-2026_image__2.2.2_sub_anti_2026_gh6oxy.webp","url2x":null,"width":1200,"height":1200}},"horizons":[{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a796","name":"2.2.2 - 25-year horizon","slug":"2-2-2-25-year-horizon","intro":{"text":"Polygenic editing erodes boundaries between therapy and enhancement"},"description":{"text":"In vitro derived gametes can be edited safely before implantation. Many forms of gene editing are mainstream. It becomes possible to engineer protection from radiation, chemical warfare and infectious diseases by altering single genes, enabling military applications as well as casual space travel. We use gene technologies to correct, slow down or even reverse processes linked to premature ageing to increase healthspan. A sleep-shortening gene is the first popular enhancement. Up- and down-regulating some specific genetic elements enhances some aspects of cognition."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89c","name":"25-year horizon","slug":"25-year-horizon","years":25,"title":"25-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a795","name":"2.2.2 - 10-year horizon","slug":"2-2-2-10-year-horizon","intro":{"text":"Safer germline editing blurs boundaries between therapy and prevention"},"description":{"text":"Inhaled and other new delivery methods move into the clinic. Epigenome editing has its first trials, targeting chronic diseases. New non-viral delivery techniques reduce the need for large doses, also reducing cost. Adenosine transversion editors expand the capabilities and applications of base editing.[38](/citation/2025-02-2-2-38/) Heritable gene editing begins to gain limited acceptance, although not everywhere, as a consequence of successful somatic techniques and preclinical safety data. Base and prime editing enable in vivo therapeutics, bringing costs of therapy down."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89b","name":"10-year horizon","slug":"10-year-horizon","years":10,"title":"10-year","subtitle":"horizon"},"embeds":{"citations":[{"slug":"2025-02-2-2-38","url":"https://doi.org/10.1038/s41587-023-01821-9","name":"Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos","authors":[{"id":"691a789fc0043bba84a9df0b","name":"L. Chen et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Nature Biotechnology","accessDate":null,"startPage":638,"volume":42,"footnoteNumber":38,"year":null}]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a794","name":"2.2.2 - 5-year horizon","slug":"2-2-2-5-year-horizon","intro":{"text":"Ex vivo and in vivo therapies advance"},"description":{"text":"More large-scale phase-III clinical trials for ex vivo therapies take place, with more therapeutics approved and commercially licensed.[32](/citation/2025-02-2-2-32/) Patient data shows mid-stage results of CRISPR-based haemophilia and retinitis pigmentosa therapies now in trials.[33](/citation/2025-02-2-2-33/),[34](/citation/2025-02-2-2-34/) Early-stage clinical trials of in vivo editing techniques, targeting easily accessible tissues such as the eye[35](/citation/2025-02-2-2-35/) or the liver, show results. In vivo therapies move to experimental clinics. CRISPR corrects for mitochondrial genetic disease in IVF procedures. Next-generation “one-shot” genome editors in vivo show long-term safety data in clinical trials.[36](/citation/2025-02-2-2-36/) Duchenne muscular dystrophy trial uses base editing to get into major tissues.[37](/citation/2025-02-2-2-37/)"},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89a","name":"5-year horizon","slug":"5-year-horizon","years":5,"title":"5-year","subtitle":"horizon"},"embeds":{"citations":[{"slug":"2025-02-2-2-32","url":"https://www.pharmaceutical-technology.com/features/crispr-gene-therapies-is-2023-a-milestone-year-in-the-making/","name":"CRISPR Gene Therapies: Is 2023 a Milestone Year in the Making?","authors":[{"id":"65c55c9b9e947c43869898ce","name":"A. Zamecnik"}],"authorShowsEtAl":null,"edition":null,"publication":"Pharmaceutical Technology","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":32,"year":null},{"slug":"2025-02-2-2-33","url":"https://www.fda.gov/vaccines-blood-biologics/roctavian","name":"Approval of roctavian to treat haemophilia","authors":[{"id":"691a788ec0043bba84a9de9b","name":"US Food and Drug Administration"}],"authorShowsEtAl":null,"edition":null,"publication":"fda.gov","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":33,"year":null},{"slug":"2025-02-2-2-34","url":"https://doi.org/10.1186/s13287-022-03036-2","name":"Generation of an MESC Model with a Human Hemophilia B Nonsense Mutation via CRISPR/Cas9 Technology","authors":[{"id":"691a789dc0043bba84a9df01","name":"Y. Ma et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Stem Cell Research & Therapy","accessDate":null,"startPage":353,"volume":13,"footnoteNumber":34,"year":null},{"slug":"2025-02-2-2-35","url":"https://www.mayoclinic.org/medical-professionals/ophthalmology/news/potential-one-time-gene-therapy-treatment-for-wet-age-related-macular-degeneration/mac-20551865","name":"Potential one-time gene therapy treatment for wet age-related macular degeneration","authors":[{"id":"66f4d38809a10d3d0e148d0a","name":"Mayo Clinic"}],"authorShowsEtAl":null,"edition":null,"publication":"mayoclinic.org","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":35,"year":null},{"slug":"2025-02-2-2-36","url":"https://www.nature.com/articles/d41586-023-03543-z","name":"First trial of ‘base editing’ in humans lowers cholesterol — but raises safety concerns","authors":[{"id":"66f4d38909a10d3d0e148d0e","name":"M. Naddaf"}],"authorShowsEtAl":null,"edition":null,"publication":"Nature","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":36,"year":null},{"slug":"2025-02-2-2-37","url":"https://doi.org/10.1073/pnas.2004840117","name":"Toward the correction of muscular dystrophy by gene editing","authors":[{"id":"66f4d38909a10d3d0e148d12","name":"E. Olson"}],"authorShowsEtAl":null,"edition":null,"publication":"Proc Natl Acad Sci","accessDate":null,"startPage":2004840117,"volume":118,"footnoteNumber":37,"year":null}]}}],"indicatorValues":[{"id":"65c55cf49e947c438698aa98","value":"0.464","numericValue":0.464,"year":2024,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}},{"id":"68edda1eaf9e6d6d63270dbb","value":"0.580","numericValue":0.58,"year":2025,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}}],"embeds":{"citations":[{"slug":"2025-02-2-2-19","url":"https://doi.org/:10.1016/j.ymthe.2023.06.013","name":"Retained chromosomal integrity following CRISPR-Cas9-based mutational correction in human embryos","authors":[{"name":"B. Bekaert et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Molecular Therapy","accessDate":null,"startPage":2326,"volume":31,"footnoteNumber":19,"year":null},{"slug":"2025-02-2-2-20","url":"https://doi.org/10.1016/j.cell.2023.08.041","name":"Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells","authors":[{"name":"C. A. Tsuchida et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Cell","accessDate":null,"startPage":4567,"volume":186,"footnoteNumber":20,"year":null},{"slug":"2025-02-2-2-21","url":"https://doi.org/10.1038/s41589-024-01595-4","name":"Engineering APOBEC3A deaminase for highly accurate and efficient base editing","authors":[{"name":"L. Yang et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Nat Chem Biol","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":21,"year":null},{"slug":"2025-02-2-2-22","url":"https://doi.org/10.1016/j.cell.2023.11.035","name":"Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA","authors":[{"name":"S-I. Cho et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Cell","accessDate":null,"startPage":95,"volume":187,"footnoteNumber":22,"year":null},{"slug":"2025-02-2-2-23","url":"https://doi.org/10.1186/s13059-024-03257-z","name":"Enhancing prime editor flexibility with coiled-coil heterodimers","authors":[{"name":"S. Mu et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Genome Biology","accessDate":null,"startPage":108,"volume":25,"footnoteNumber":23,"year":null},{"slug":"2025-02-2-2-24","url":"https://doi.org/10.1038/s41588-023-01434-7","name":"Potent and uniform fetal hemoglobin induction via base editing","authors":[{"name":"T. Mayuranathan et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Nature Genetics","accessDate":null,"startPage":1210,"volume":55,"footnoteNumber":24,"year":null},{"slug":"2025-02-2-2-25","url":"https://doi.org/10.1038/s41551-023-01026-0","name":"Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice","authors":[{"name":"K. A. Everette et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Nature Biomedicine","accessDate":null,"startPage":616,"volume":7,"footnoteNumber":25,"year":null},{"slug":"2025-02-2-2-26","url":"https://doi.org/10.1182/blood.2022018252","name":"In vivo HSC prime editing rescues sickle cell disease in a mouse model","authors":[{"name":"C. Li et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Blood","accessDate":null,"startPage":2085,"volume":141,"footnoteNumber":26,"year":null},{"slug":"2025-02-2-2-27","url":"https://doi.org/10.1016/j.xcrm.2024.101544","name":"Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells","authors":[{"name":"M. Bulcaen et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Cell Reports Medicine","accessDate":null,"startPage":101544,"volume":5,"footnoteNumber":27,"year":null},{"slug":"2025-02-2-2-28","url":"https://doi.org/10.1038/s41587-023-02095-x","name":"Prime editing using CRISPR-Cas12a and circular RNAs in human cells","authors":[{"name":"R. Liang et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Nature Biotechnology","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":28,"year":null},{"slug":"2025-02-2-2-29","url":"https://doi.org/10.3389/fgeed.2023.1271813","name":"Reciprocal mutations of lung-tropic AAV capsids lead to improved transduction properties","authors":[{"name":"A. Cooney et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Frontiers in Genome Editing","accessDate":null,"startPage":null,"volume":5,"footnoteNumber":29,"year":null},{"slug":"2025-02-2-2-30","url":"https://doi.org/10.1007/s13346-023-01320-z","name":"Recent Advances in the Delivery and Applications of Nonviral CRISPR/Cas9 Gene Editing","authors":[{"name":"F. Sinclair et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Drug Delivery and Translational Research","accessDate":null,"startPage":1500,"volume":13,"footnoteNumber":30,"year":null},{"slug":"2025-02-2-2-31","url":"https://doi.org:10.1016/j.ajps.2023.100854","name":"CRISPR/Cas9 systems, Delivery technologies and biomedical applications","authors":[{"name":"Y. Du et al"}],"authorShowsEtAl":null,"edition":null,"publication":"Asian Journal of Pharmaceutical Science","accessDate":null,"startPage":100854,"volume":18,"footnoteNumber":31,"year":null}],"imageAssets":[]}},{"id":"65c55d4f9e947c438698b671","name":"Engineered organisms and AI-based tools","path":"/sub-topics/engineered-organisms-and-ai-based-tools","outlineNumber":"2.2.3","slug":"engineered-organisms-and-ai-based-tools","__typename":"Platform_SubTopic","color":{"id":"65c55cbc9e947c438698a325","name":"Teal","value":"#44AFCD"},"topic":{"id":"65c55d599e947c438698b7b7","slug":"cell-and-gene-engineering","path":"/topics/cell-and-gene-engineering"},"intro":{"text":"AI promises to accelerate drug discovery.[39](/citation/2025-02-2-2-39/) Synthetic organisms and AI will help advance genome editing for human applications in several crucial ways, including improved ways to deliver the editing payload to the cell and experimental organisms that provide a better proxy for human testing. [40](/citation/2025-02-2-2-40/)"},"description":{"text":"AI will help to quickly scan whole genomes and then design vectors that can be used more universally. Work is also under way in AI design of entirely new proteins and editors.[41](/citation/2025-02-2-2-41/) However, human screeners are still needed to identify the small percentage that will work as they are meant to. This situation may improve with access to more training data. Generally, advances here will require more collaboration between mathematicians and biologists.\n\nFurthermore, machine-learning algorithms may help identify the relationships among genes, gene networks and other variables (such as epigenetic factors) involved in disease, as well as the potential consequences of edits to these.[42](/citation/2025-02-2-2-42/) AI-enabled searches through microbial data obtained from uncultivated samples may reveal more suitable enzymes — helicases, nucleases, transposases or recombinases — that solve the problems of currently available editors. \n\nRecent rapid advances in stem-cell engineering, stem-cell-derived embryo models, organoids (artificial and simplified versions of an organ) and tissue engineering are helping research move towards providing experimental organisms based on human physiology that will help predict the functionalities of genome editors outside the human body and before clinical applications.[43](/citation/2025-02-2-2-43/),[44](/citation/2025-02-2-2-44/)"},"anticipationScores":{"text":"The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate: \n\n1. The *uncertainty* related to future science breakthroughs in the field\n2. The *transformative* *effect* anticipated breakthroughs may have on research and society\n3. The *scope for action* in the present in relation to anticipated breakthroughs. \n\nThis chart represents a summary of their responses to each of these elements, which when combined, provide the *Anticipation Potential* for the topic. See [methodology](/science-anticipation/methodology) for more information."},"anticipationScoresImage":{"id":"68e89fe963d1c853e9788ca5","image":{"id":"image_gesda-platform/image-asset/2-2-3-sub-anti-2026_image__2.2.3_sub_anti_2026_hhuwo5","url":"https://res.cloudinary.com/shapeable/image/upload/v1760075738/gesda-platform/image-asset/2-2-3-sub-anti-2026_image__2.2.3_sub_anti_2026_hhuwo5.webp","url2x":null,"width":1200,"height":1200}},"horizons":[{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a799","name":"2.2.3 - 25-year horizon","slug":"2-2-3-25-year-horizon","intro":{"text":"Universal editors emerge"},"description":{"text":"Engineered cells and tissues are grafted into complex tissues like the brain or the endocrine system. With prime and base editing, plus tissues grown outside the body and reimplanted, modification becomes easier and cheaper, rivalling in vivo. Genetically modified viruses, synthetic viruses and large genetic circuits are widely deployed for pre-emptive “gene surgery” on otherwise healthy people, directly linking genetic circuits to genome editors. We see the first demonstration in humans of universal cells carrying gene circuitry."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89c","name":"25-year horizon","slug":"25-year-horizon","years":25,"title":"25-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a798","name":"2.2.3 - 10-year horizon","slug":"2-2-3-10-year-horizon","intro":{"text":"Chimeras, synthetic viruses and other models become mainstream"},"description":{"text":"Synthetic biology circuits, now in mammalian cell cultures, find applications in vivo and for enhanced control of genome editors for gene therapies. Chimeras generated by injecting human stem cells into animal embryos grow organs for xenotransplantation or grow human-like brain structures to study the effects of gene edits. Improved synthetic viruses and genome editors knock out genes in animal organs to supply the increasing need for human organ donation without the risk of rejection. Engineered cells and tissues serve as novel delivery systems to easily grafted tissues such as bone and skin."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89b","name":"10-year horizon","slug":"10-year-horizon","years":10,"title":"10-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a797","name":"2.2.3 - 5-year horizon","slug":"2-2-3-5-year-horizon","intro":{"text":"Synthetic biology circuits go in vivo"},"description":{"text":"Extremely rapid progress in machine learning and AI solves many obstacles to engineering proteins and enzymes. AI helps create de novo gene editor. Genome reading and writing allows us to build large genetic circuits composed of many repeated guide RNA sequences that enable us to simultaneously target multiple genes. AI leads to engineered proteins and enzymes."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89a","name":"5-year horizon","slug":"5-year-horizon","years":5,"title":"5-year","subtitle":"horizon"},"embeds":{"citations":[]}}],"indicatorValues":[{"id":"65c55cf49e947c438698aabf","value":"0.512","numericValue":0.512,"year":2024,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}},{"id":"68edda4baf9e6d6d63270dca","value":"0.610","numericValue":0.61,"year":2025,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}}],"embeds":{"citations":[{"slug":"2025-02-2-2-39","url":"https://www.gene.com/stories/redefining-drug-discovery-with-ai","name":"Redefining Drug Discovery with AI","authors":[{"name":"Genentech"}],"authorShowsEtAl":null,"edition":null,"publication":"gene.com","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":39,"year":null},{"slug":"2025-02-2-2-40","url":"https://www.science.org/content/article/better-crispr-another-way-fix-gene-problems-may-be-safer-and-more-versatile","name":"Better than CRISPR? Another way to fix gene problems may be safer and more versatile","authors":[{"name":"J. Kaiser"}],"authorShowsEtAl":null,"edition":null,"publication":"Science","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":40,"year":null},{"slug":"2025-02-2-2-41","url":"https://doi.org/10.1038/s41587-022-01624-4","name":"A Universal Deep-Learning Model for Zinc Finger Design Enables Transcription Factor Reprogramming","authors":[{"name":"D. M. Ichikawa et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Nature Biotechnology","accessDate":null,"startPage":1,"volume":26,"footnoteNumber":41,"year":null},{"slug":"2025-02-2-2-42","url":"https://doi.org/10.3389/fpls.2018.01770","name":"Statistical and Machine Learning Approaches to Predict Gene Regulatory Networks From Transcriptome Datasets","authors":[{"name":"K. Mochida et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Frontiers in Plant Science","accessDate":null,"startPage":null,"volume":9,"footnoteNumber":42,"year":null},{"slug":"2025-02-2-2-43","url":"https://doi.org/10.1038/s41586-021-03191-1","name":"The NIH Somatic Cell Genome Editing Program","authors":[{"name":"K. Saha et al."}],"authorShowsEtAl":null,"edition":null,"publication":"Nature","accessDate":null,"startPage":195,"volume":592,"footnoteNumber":43,"year":null},{"slug":"2025-02-2-2-44","url":"https://www.theguardian.com/science/2022/aug/03/scientists-create-worlds-first-synthetic-embryos","name":"Scientists Create World’s First ‘Synthetic Embryos’","authors":[{"name":"I. Sample"}],"authorShowsEtAl":null,"edition":null,"publication":"The Guardian","accessDate":null,"startPage":null,"volume":null,"footnoteNumber":44,"year":null}],"imageAssets":[]}},{"id":"65c55d4f9e947c438698b650","name":"Alternatives to direct gene editing","path":"/sub-topics/alternatives-to-direct-gene-editing","outlineNumber":"2.2.4","slug":"alternatives-to-direct-gene-editing","__typename":"Platform_SubTopic","color":{"id":"65c55cbc9e947c438698a325","name":"Teal","value":"#44AFCD"},"topic":{"id":"65c55d599e947c438698b7b7","slug":"cell-and-gene-engineering","path":"/topics/cell-and-gene-engineering"},"intro":{"text":"Existing approaches to gene editing are all-or-nothing: gene sequences are altered, removed or added. However, some diseases manifest through inadequate gene expression that is dialled too far up or down rather than turned on or off. This means that, in some cases, techniques such as editing the epigenome may be a better option.[45](/citation/2025-02-2-2-45/) Simply adding or removing the chemical tags that adorn DNA, for instance, could dial down or up expression of certain genes or variants without the risk of dangerous mutations. Epigenetic mechanisms include histone modifications and DNA methylation; manipulating the factors that control these can be both tuneable and reversible, and could be especially useful for controlling more than one gene.[46](/citation/2025-02-2-2-46/) Once considered a dark art, epigenome editing is now rapidly advancing.[47](/citation/2025-02-2-2-47/)"},"description":{"text":"Another approach, editing RNA, could open up much more common diseases like chronic pain. Some drugs are already in clinical trials."},"anticipationScores":{"text":"The Anticipation Potential of a research field is determined by the capacity for impactful action in the present, considering possible future transformative breakthroughs in a field over a 25-year outlook. A field with a high Anticipation Potential, therefore, combines the potential range of future transformative possibilities engendered by a research area with a wide field of opportunities for action in the present. We asked researchers in the field to anticipate: \n\n1. The *uncertainty* related to future science breakthroughs in the field\n2. The *transformative* *effect* anticipated breakthroughs may have on research and society\n3. The *scope for action* in the present in relation to anticipated breakthroughs. \n\nThis chart represents a summary of their responses to each of these elements, which when combined, provide the *Anticipation Potential* for the topic. See [methodology](/science-anticipation/methodology) for more information."},"anticipationScoresImage":{"id":"68e89e5063d1c853e9788c84","image":{"id":"image_gesda-platform/image-asset/2-2-4-sub-anti-2026_image__2.2.4_sub_anti_2026_wfiyay","url":"https://res.cloudinary.com/shapeable/image/upload/v1760075330/gesda-platform/image-asset/2-2-4-sub-anti-2026_image__2.2.4_sub_anti_2026_wfiyay.webp","url2x":null,"width":1200,"height":1200}},"horizons":[{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a79c","name":"2.2.4 - 25-year horizon","slug":"2-2-4-25-year-horizon","intro":{"text":"Cosmetic gene editing becomes possible"},"description":{"text":"Delivery methods of enzymes and editors — whether gene or epigenome — become straightforward and open to dynamic control. Epigenome editing helps people temporarily mute some genes or express others, making for temporary alterations including military night vision and resistance to radiation, viruses and chemical weapons. Cosmetic mutations, such as temporary eye-colour changes, are popular in body-hacking subcultures. Fundamental alterations to the microbiome make humans capable of digesting cellulose or extracting nutrition from plastic."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89c","name":"25-year horizon","slug":"25-year-horizon","years":25,"title":"25-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a79b","name":"2.2.4 - 10-year horizon","slug":"2-2-4-10-year-horizon","intro":{"text":"Epigenome editors are fine-tuned"},"description":{"text":"Metagenomics becomes a standard tool for microbial ecology laboratories, using methods similar to gene fingerprinting to profile microbial communities. Epigenome editing becomes titratable."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89b","name":"10-year horizon","slug":"10-year-horizon","years":10,"title":"10-year","subtitle":"horizon"},"embeds":{"citations":[]}},{"__typename":"Platform_Horizon","id":"65c55ce69e947c438698a79a","name":"2.2.4 - 5-year horizon","slug":"2-2-4-5-year-horizon","intro":{"text":"Disease spread is monitored through metagenomics"},"description":{"text":"Metagenomics advances make it possible to monitor the emergence (or re-emergence) of viral diseases with the goal of containing their spread. Epigenome editors alter epigenetic state at precise locations within the genome, lowering the chance of immune response, and are fine-tuned for first use on disease genes and tissues, and tested in vivo. New sequencing methods identify epigenetic modifications while preserving the accuracy of genome sequencing. Insights are gained into how interventions like diet and exercise alter gut microbiome."},"color":{"__typename":"Platform_Color","id":"65c55cbc9e947c438698a325","name":"Teal","slug":"teal","value":"#44AFCD"},"type":{"__typename":"Platform_HorizonType","id":"65c55ce79e947c438698a89a","name":"5-year horizon","slug":"5-year-horizon","years":5,"title":"5-year","subtitle":"horizon"},"embeds":{"citations":[]}}],"indicatorValues":[{"id":"65c55cf49e947c438698ab01","value":"0.476","numericValue":0.476,"year":2024,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}},{"id":"68edda77af9e6d6d63270dd9","value":"0.600","numericValue":0.6,"year":2025,"indicator":{"id":"65c55cf29e947c438698aa4d","name":"Anticipation Potential","title":null,"slug":"anticipation-potential","dataSetId":"ANTICIPATION_POTENTIAL","color":null}}],"embeds":{"citations":[{"slug":"2025-02-2-2-45","url":"https://www.science.org/content/article/better-crispr-another-way-fix-gene-problems-may-be-safer-and-more-versatile","name":"Better than CRISPR? Another Way to Fix Gene Problems May Be Safer and More Versatile","authors":[{"name":"J. Kaiser"}],"authorShowsEtAl":null,"edition":null,"publication":"Science","accessDate":null,"startPage":1034,"volume":376,"footnoteNumber":45,"year":null},{"slug":"2025-02-2-2-46","url":"https://www.sciencedirect.com/science/article/pii/S0092867421003536","name":"Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing","authors":[{"name":"J.K. Nuñez"}],"authorShowsEtAl":null,"edition":null,"publication":"Cell","accessDate":null,"startPage":2503,"volume":184,"footnoteNumber":46,"year":null},{"slug":"2025-02-2-2-47","url":"https://doi.org/10.21769/BioProtoc.4976","name":"CRISPR/dCas9-Tet1-Mediated DNA Methylation Editing","authors":[{"name":"J. Qian and S. X. Liu"}],"authorShowsEtAl":null,"edition":null,"publication":"Bio Protocol","accessDate":null,"startPage":4976,"volume":14,"footnoteNumber":47,"year":null}],"imageAssets":[]}}],"committeeMembers":[{"__typename":"Platform_Person","id":"65c55d249e947c438698b07d","name":"Alejandro Chavez","slug":"alex-chavez","position":"Professor","path":"/people/alejandro-chavez","badge":"2025","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"65c55d5b9e947c438698b7c5","name":"Alejandro Chavez||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"},{"id":"66ab1bac36a8f2f336a557ba","name":"2023","slug":"2023"},{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024"},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b0e2","name":"David Liu","slug":"david-liu","position":"Global Expert","path":"/people/david-liu","badge":"2022","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"65c55d5b9e947c438698b7e1","name":"||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-1","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b0f5","name":"Effy Vayena","slug":"effy-vayena","position":"Professor of Bioethics","path":"/people/effy-vayena","badge":"2022","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"65c55d5b9e947c438698b7e9","name":"||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-2","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b11f","name":"George Church","slug":"george-church","position":"Professor of Genetics","path":"/people/george-church","badge":"2022","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"65c55d5b9e947c438698b7f6","name":"||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-3","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b141","name":"Isabelle Mansuy","slug":"isabelle-mansuy","position":"Professor\n","path":"/people/isabelle-mansuy","badge":"2025","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"66f9f76d0c1d37f97d91ef88","name":"Isabelle Mansuy||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-5","editions":[{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024"},{"id":"66ab1bac36a8f2f336a557ba","name":"2023","slug":"2023"},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b185","name":"Kelly Ormond","slug":"kelly-ormond","position":"Professor","path":"/people/kelly-ormond","badge":"2025","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"66f9f78f0c1d37f97d91ef9a","name":"Kelly Ormond||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-6","editions":[{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024"},{"id":"66ab1bac36a8f2f336a557ba","name":"2023","slug":"2023"},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b188","name":"Krishanu Saha","slug":"krishanu-saha","position":"Global Expert","path":"/people/krishanu-saha","badge":"2022","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"65c55d5b9e947c438698b81d","name":"||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-4","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b202","name":"Philip M. Kim","slug":"philip-m-kim","position":"Professor","path":"/people/philip-m-kim","badge":"2025","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"66f9f8320c1d37f97d91f30e","name":"Philip M. Kim||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-member-human-applications-of-genetic-engineering-7","editions":[{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024"},{"id":"66ab1bac36a8f2f336a557ba","name":"2023","slug":"2023"},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]},{"__typename":"Platform_Person","id":"65c55d249e947c438698b230","name":"Samira Kiani","slug":"samira-kiani","position":"Co-Founder","path":"/people/samira-kiani","badge":"2025","color":{"value":"#44AFCD"},"topicExpertise":[{"id":"66daae4360475bb85b1124f1","name":"Samira Kiani||Anticipation Committee Member|Human Applications of Genetic Engineering","slug":"anticipation-committee-chair-human-applications-of-genetic-engineering-1","editions":[{"id":"66ab1ba336a8f2f336a557b5","name":"2022","slug":"2022"},{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]}],"committeeChairs":[{"__typename":"Platform_Person","id":"65c55d249e947c438698b223","name":"Robin Lovell-Badge","slug":"robin-lovell-badge","position":"Principal Group Leader, Stem Cell Biology and Developmental Genetics Laboratory","path":"/people/robin-lovell-badge","openGraph":{"id":"openGraph_person/robin-lovell-badge","title":"Robin Lovell-Badge","image":{"id":"image_gesda-platform/person/robin-lovell-badge_photo__Robin-Lovell-Badge_l7aryk","url":"https://res.cloudinary.com/shapeable/image/upload/v1726018057/gesda-platform/person/robin-lovell-badge_photo__Robin-Lovell-Badge_l7aryk.png","url2x":null,"thumbnails":{"card":{"id":"thumbnails-card-file_gesda-platform/person/robin-lovell-badge_photo__Robin-Lovell-Badge_l7aryk","url":"https://res.cloudinary.com/shapeable/image/upload/c_limit,w_480/v1726018057/gesda-platform/person/robin-lovell-badge_photo__Robin-Lovell-Badge_l7aryk.png","url2x":"https://res.cloudinary.com/shapeable/image/upload/c_limit,w_960/v1726018057/gesda-platform/person/robin-lovell-badge_photo__Robin-Lovell-Badge_l7aryk.png"}}}},"organisation":{"id":"65c55d059e947c438698ac56","name":"Francis Crick Institute","slug":"francis-crick-institute"},"topicExpertise":[{"id":"66f9f6be0c1d37f97d91ef4e","name":"||Anticipation Committee Chair|Human Applications of Genetic Engineering","slug":"anticipation-committee-chair-human-applications-of-genetic-engineering","editions":[{"id":"66ab1bb636a8f2f336a557bf","name":"2024","slug":"2024"},{"id":"66ab1bac36a8f2f336a557ba","name":"2023","slug":"2023"}],"topic":{"id":"65c55d599e947c438698b7b7"}},{"id":"68b0f94d1dec39db691be2aa","name":"Robin Lovell-Badge||Anticipation Committee Chair|Organoids","slug":"robin-lovell-badge-anticipation-committee-chair-organoids","editions":[{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7ba"}},{"id":"68b3da6f3a80dfdcfcb35896","name":"Robin Lovell-Badge||Anticipation Committee Chair|Human Applications of Genetic Engineering","slug":"robin-lovell-badge-anticipation-committee-chair-human-applications-of-genetic-engineering","editions":[{"id":"684951c963371e51d83bdf31","name":"2025","slug":"2025"}],"topic":{"id":"65c55d599e947c438698b7b7"}}]}]}}},"pageContext":{"id":"65c55d599e947c438698b7b7","name":"Cell and Gene Engineering","slug":"cell-and-gene-engineering","entityPath":"/topics/cell-and-gene-engineering","entityTypeName":"Topic","__type":"Topic"}},
    "staticQueryHashes": ["1044227382","1071300789","1158597448","1242646999","1427075558","1452322194","1520036161","1586309863","1606754935","1734835243","1816168740","1903214493","1989845544","2034981229","2097402925","2181044613","239250450","2409034939","2463401854","2612382444","2862279633","2910164142","2912920178","2955142335","3005265507","3073584486","3124191253","3172506128","3320076387","3624873332","364221563","3665990662","3692255024","3778988535","3782604890","4091857177","4216505212","701411134","758936535","881103158"]}