CRISPR-Cas9 complex with guide RNA and DNA primed for cleavage

Dr Stephen Chambers, CEO SynbiCITE

According to the Boston Consulting Group in the past two years over one billion dollars has been invested in start-up companies looking to exploit the new genome editing technique utilising the CRISPR (clustered, regularly interspaced short palindromic repeats)-Cas9 system. One reason for the phenomenal rise of CRISPR-Cas9 is the simplicity of the system, consisting of just two elements: a guide RNA, which binds the targeted DNA, and the DNA cutting nuclease Cas9, which complexes with the guide RNA. Both elements can be delivered into cells with a single vector expressing both the Cas9 protein and the guide RNA sequence. The CRISPR-Cas9 system has revolutionised the way genome sequences are edited and manipulated, rapidly becoming an indispensable tool in research labs around the world. This has been reflected by the 20 papers/week published on CRISPR-Cas9 during 2015. What has been more interesting though is how this technology is now finding an application as a therapeutic.

Despite potential technical problems with off-target activity and a murky IP landscape, a number of start-ups are looking to commercially exploit this exciting technology as a new kind of medicine. New gene-editing companies have been raising large rounds (some filing IPOs) and been striking big deals with companies with Chimeric Antigen Receptor (CAR) T-cells therapy projects in development. The list of deals includes: Editas Medicine & Juno Therapeutics, CRISPR Therapeutics & Celgene /GSK, Intellia Therapeutics & Novartis, and Cellectis & Pfizer. CAR-T cells are engineered to express an artificial receptor, which binds to a specific antigen on the surface of cancer cells, directing the body’s own immune system to recognise and attack tumours. T-cell engineering using transgenesis is now being replaced with CRISPR-Cas9 allowing gene editing to remove proteins that activate the immune response. This opens up the potential of engineering allogeneic CAR-T cells, derived from a single healthy donor and used to treat thousands of patients – creating a safe and efficient means of cancer treatment.

It is highly likely that in the therapeutic area, gene-editing technology will make its initial breakthrough engineering CAR-T cells in cancer immunotherapy. This is significant, since according to the ACS 2015 annual report; cancer will overtake heart disease as the leading cause of deaths. The number of new cancer cases is expected to increase nearly 45% by 2030. This influx of new patients will place a bigger burden on a health service already stretched by physician shortages and financial difficulties, says the report, which highlights growing problems for cancer care. A breakthrough cancer treatment based on engineering biology could have a dramatic impact on the future landscape of healthcare.