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. 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.27
Another emerging option is precision microbiome editing:28 recent insights make it clear that these microorganisms play key roles in diseases. Current tools are blunt and ineffective, but it should be possible to exert precise control over the microbiome using CRISPR and metagenomics.29 Electrogenetic systems — electrochemical or electrical interfaces — can also activate or repress gene expression in tuneable ways.30 Pre-clinical studies show this method can control glycemic levels in diabetic mice.31 The key to future progress is metagenomics, which can provide a complete profile of all the diverse organisms in a given microbiome and is becoming more affordable.32
