Guest blog: CRISPR /Cas9: Therapeutic revolution, or merely a drug discovery tool?

Author – Dr Jon Moore, Chief Scientific Officer and Head of Translational Science, Horizon Discovery

CRISPR made another break out from the technical literature to the popular press this month with a story about mice with skin grafts engineered to express the insulin regulating hormone GLP1.

Xiaoyang Wu’s group at the University of Chicago published an impressive paper in Cell Stem Cell where they reported the engineering of epidermal stem cells to express a long half-life version of glucagon-like peptide 1 (GLP1). After engraftment in immunologically compatible mice, the skin grafts were able to increase insulin levels and reduce the weight gain and insulin resistance imposed by a high fat diet.

Exciting news, but is this technology likely to be deployed in the treatment of type 2 diabetes any time soon? It seems doubtful. While discovery phase research with gene editing technology might be cheaper than a typical medicinal chemistry project, the costs incurred in development will likely be similar, and the cost of goods much higher than small molecule drugs or biologicals. Skin grafts would ideally need to be autologous to avoid the need for immunosuppressants, which would mean a labour intensive process of stem cell isolation and engineering has to be performed for each patient. For an indication as prevalent as diabetes, these costs would seem to be crippling.

However, for rarer life-threatening indications where small molecule drugs and biologics have limited impact, the regulatory barriers and economics look far more favourable, especially for gene editing therapies that can provide long-term or lifelong treatments. Particularly if these treatments can be delivered in vivo, rather than through the ex-vivo editing of cells, then the cost per patient will be considerably reduced although there are likely to be significant up-front costs associated with the discovery and development of the treatment.

With the rapid pace of advances in CRISPR/Cas9, the economic and regulatory barriers to the wide deployment of gene therapy and gene editing currently appear to be greater than the technical challenges of discovery and development. Hence an argument can be made that the greatest immediate impact of this technology on patients will come from productivity increases that it is bringing to drug discovery, both for its use in target ID and validation, and in the greater resolution and understanding it allows of biological and pathological processes in academic research.

Note: Horizon is hosting a meeting in Dublin on 17-18 October, bringing together leaders in the field of CRISPR to explore the potential for advances in drug development and therapeutics brought about by progress in gene editing technology. With a substantial proportion of the oral programme given over to talks selected from submitted abstracts to discuss innovative ideas, and a focus on closing the gap between new developments in CRISPR technology and application in life sciences, we hope that the CRISPR Forum will be an exciting event for anyone working in the field. More information on the programme and how to register can be found here.