Novel gene-editing platforms like base and prime editing³ and new delivery methods including lentiviral vectors, have treated a wide range of genetic blood disorders,⁴ which now opens the door to broader applications of cell and gene therapies. After the success of mRNA vaccines, other RNA-based therapies are being explored, including antisense oligonucleotides (ASO), which bind to RNA targets, preventing them from producing harmful proteins, such as those which cause Huntington’s Disease in the brain.⁵

Future Horizons:

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5-yearhorizon

Editing gets specific

Gene-transfer technologies, including AAV vectors and lipid nanoparticles, are repurposed to deliver epigenetic effectors. First human trials begin for gene therapy that targets only affected neurons, treating treatment-resistant epilepsy.⁹,¹⁰ Oligonucleotides are approved to target more rare diseases. Clinical trials on RNA antisense therapeutics reveal whether the therapy can help people with ALS and other neurodegenerative diseases.

10-yearhorizon

Delivery gets specific

First human trials on gene therapy against Parkinson’s disease that targets excitability in ion channels in neuronal circuits begin.¹¹ Non-viral delivery methods succeed in inserting payloads into the DNA-containing nucleus of the cell. Lentiviral vectors combined with CRISPR-Cas9 and other gene-engineering tools becomes a way to destroy solid tumours. The range of clinical indications for bone-marrow-derived stem-cell-based gene therapies expands widely; allogeneic hematopoietic-stem-cell transplantation (HSPC) is phased out in favour of autologous gene therapy.

25-yearhorizon

Selectivity gets specific and therapies become general

Glycosylation or other metabolic markers offer more specific targets for immune-cell-based therapy.¹² Research pivots towards editing and delivery methods that can be batch-produced for many patients across different diseases. Engineered-immune-cell therapies such as those using CAR-T cells become standardised.

The next frontier is selectivity. The health risks of taking immune cells out of patients for editing can be avoided with therapies that act directly on tissues within the body. But these rely on the ability to ferry gene editors into specific tissues or cells. The most commonly used viral delivery method, adeno-associated virus (AAV), can reach accessible tissues such as the eyes and blood, but have more difficulty in penetrating muscle, specific locations in the brain and solid tumours.⁶ However, new site-specific gene-editing methods can infiltrate tumours and preferentially target brain areas linked to focal epilepsy.⁷ Engineered immune cells can now contain logic gates that selectively target leukaemia cells.⁸ Other disease-sensitive approaches could target metabolic signatures of diseased cells.

To affordably advance regenerative medicine, immunotherapy and cancer therapies requires moving from personalised therapies to greater generalisation.

Future cell and gene therapy - Anticipation Scores

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:

The uncertainty related to future science breakthroughs in the field
The transformative effect anticipated breakthroughs may have on research and society
The scope for action in the present in relation to anticipated breakthroughs.

This chart represents a summary of their responses to each of these elements, which when combined, provide the Anticipation Potential for the topic. See methodology for more information.