Genome editing: a broad perspective on a precision technology – PHG Foundation

Genome editing goes prime-time

Genome editing was in the news again recently, following the publication of a paper that describes prime-editing, a new method of altering genetic information. Whilst more information is needed to accurately assess the true potential of this technique, prime-editing does represent another addition to the ever-growing suite of genome editing tools many of which will have an impact on treatment approaches to genetic diseases. In our latest set of policy briefings, we outline the current state of somatic genome editing in health, discussing areas of greatest progress, limitations and the evolving regulatory landscape and ethical considerations surrounding its application.

Genome editing describes a suite of techniques that can be used to alter genetic sequences. These all use a cutting enzyme and a targeting mechanism to make cuts and induce repair in DNA, altering the genetic sequence in the process. CRISPR-Cas has received the greatest attention in recent years, owing to its precision and relative ease of use.

The new technique prime-editing differs from standard CRISPR-Cas by making a cut in only one of the two DNA strands and using different methods to induce repair and add new information to the DNA. The technique could potentially be used to make alterations in genomic regions which preceding techniques cannot. However, it also has its limitations.

The hype surrounding both somatic and germline genome editing has reflected the general excitement and rapid progress in a field that stole the spotlight in 2012, thanks to the arrival of CRISPR-Cas9 for DNA editing. While germline editing is still being hotly debated, and dominates the headlines, greater awareness is needed of the current scope and applicability of somatic genome editing for health, and the broader progress that is being made in addressing genetic disease. The focus on human germline editing has somewhat obscured the impacts of somatic gene editing on individuals and populations.

Several therapies based on genome editing techniques in somatic cells have now made their way into clinical trials, including several therapies for rare blood disorders such as sickle cell disease and retinal disorders such as Leber congenital amaurosis. Genome editing is also having an impact on therapies and diagnostics beyond its direct applications for rare disease; for instance, CAR-T therapies a type of immunotherapy for blood cancer and in research into cancer diagnostics that utilise CRISPR for detecting the presence of genetic variants.

Like all disruptive technologies, somatic genome editing poses legal and ethical challenges, which should be considered alongside the potentially life-changing benefits for patients. Although somatic editing physically impacts only the individual whose cells are edited, its use could still have wide-reaching societal implications. For example, genome editing in one individual will inevitablyhave an impact upon other patients may be stigmatised or discriminated against if they are unable or unwilling to recieve the same therapy. The circumstances in which genome editing is used will also have an impact upon public views of the technology, as studies show that whilst there is widespread support for genome editing for therapeutic applications, this does not extend to non-therapeutic use. High-profile cases may further influence this view one way or another.

Although the drive to develop genome editing comes predominantly from therapeutic need, these techniques could theoretically be put to non-therapeutic use i.e. enhancement. Much policy and public discussion assumes a meaningful distinction between the two. But in recent years, as preventative health has taken centre stage, this distinction has become harder to maintain; medicine is not just about treating acute disease, its about identifying and reacting to risk. Is editing out a mutation that carries an increased risk of developing cardiovascular disease a therapeutic intervention? Navigating this blurred line is hugely debated, and societal debate on such issues will become more important as the associated risks and benefits become clearer, influencing how genome editing might be used in the future.

Whilst momentum is building around the use of genome editing technologies, the significant journey from the bench to the bedside is often underestimated, and it can be easy to forget that current developments are built on decades of contributory research in related fields. Patients are beginning to see benefits from genome editing, but use is currently limited to a small number of rare disease and cancer patients taking part in clinical trials. However, looking to the future, new techniques such as prime-editing and base-editing could expand the applications of genome editing. There is much excitement and optimism among researchers about these techniques, but this is only the beginning in terms of exploring how they could practically be used. In time, these techniques might be used to develop new therapies, once their safety and efficacy have been established and technical obstacles such as how to deliver the editing tools to cells have been overcome. A further challenge will be to ensure that the regulatory landscape is sufficiently robust and dynamic to be able to accommodate these novel technologies.

For more information, see our policy briefings:

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Genome editing: a broad perspective on a precision technology - PHG Foundation