From theory to therapy in the genome editing boom

By Emma Johnson

21 August 2019


Last month, in her final annual report as Chief Medical Officer for England, Dame Sally Davies outlined the current status and future vision of UK involvement in global health. As a technology of global importance and considerable potential for health, genome editing received some mention. The various tools and techniques used for genome editing, which come in several forms including CRISPR, allow for permanent changes to be made to the genetic code with relative ease. As variations in DNA can play a significant (sometimes pivotal) role in health and disease, the technology could have many applications.

In the CMO’s report, Health, our global asset – partnering for progress, one of the many letters submitted by global health leaders emphasises the potential of genome editing to prevent and treat heritable diseases and other conditions such as cancer but cautions that several issues remain to be addressed before the technology is ready for clinical use. Genome editing is a technology that has been riding the wave of hype for some time, but also one that is genuinely making its way into healthcare.

The research race

The PHG Conference 2019 - From Hype to Healthcare - included a breakout session dedicated to genome editing therapies (an introduction to which can be found here). Dr Helen O’Neill and Julian Hitchcock spoke about the technology and key policy issues for health applications. Dr O’Neill discussed the unusual character of the genome editing boom, the progression of which has outpaced that of other technologies, owed in part to its advancing ease of use and broad applicability across different sectors ranging from health to agriculture and research. Dr O’Neill described a ‘nucleotidal wave’ of publications demonstrating the pace of activity in this field - around 3000 papers on CRISPR genome editing published between the end of 2018 to March 2019 alone.

Progress for patients

Although techniques for editing the genome aren’t all new, the introduction of CRISPR in 2013 brought rapid acceleration to research into genome editing based medical therapies. Six years on from its introduction to the scientific world, we have the first clinical trials using in vivo CRISPR genome editing (CRISPR-based editing that takes place inside the body) in human beings.

The first in vivo CRISPR trial in the US, a treatment for the rare eye disorder Leber Congenital Amaurosis, will involve the injection of CRISPR editing tools behind the patient’s retina to cut and induce the repair of faulty DNA that otherwise ultimately leads to blindness. The first patients are being recruited to the trial this year.

2019 has also seen the first trials of CRISPR-based cancer treatments  begin in the US, combining two highly complex technologies - genome editing and T-cell immunotherapy. In China, CRISPR-edited T-cell therapies (similar to CAR-T therapies discussed in a recent blog) are already being applied to treat patients with cancer.

Companies specialising in the production of genome editing therapies, such as CRISPR Therapeutics and Editas Medicine, are developing treatments for a broad range of conditions using the same base technologies. CRISPR Therapeutics boasts a portfolio of nine CRISPR-based therapies under development and moving into clinical trials, aimed at treating conditions ranging from common cancers to cystic fibrosis and Duchenne muscular dystrophy.

Despite the attention garnered by more controversial germline genome editing (editing that results in ‘heritable’ changes to the DNA that can be passed on to subsequent generations), by far the most significant advances are in somatic (non-heritable) editing. Nor does CRISPR, although it dominates the field, provide the whole picture - several genome editing therapies currently under investigation and moving into trials use older genome editing tools such as TALENs and ZFNs, often where research was established before the advent of CRISPR. These techniques aim to do much the same thing as CRISPR, and have their own advantages, but are in many ways harder to work with.

Editing the future

As we move forward, the list of potential applications for genome editing techniques gets longer, and the maturity of companies working with these technologies increases. New iterations of CRISPR-based editing tools including the introduction of new cutting enzymes with specific advantages (e.g. cas12b), innovative techniques to allow editing tools to enter cells, and the prospect of super-precise base-editing techniques, mean that these trends are likely to continue.

CRISPR research is also branching out into other areas of health - RNA-based diseases, novel diagnostics and drug discovery. Gene drive techniques are also finding potential applications for public health interventions; used to propagate certain genetic traits in populations, gene drive could be applied to generate sterility in female mosquitoes, the hope being to significantly reduce the prevalence of malaria.

However, as warned in the CMO’s report, concerns over unanticipated (or unintended) impacts need to be addressed before some of these techniques can be applied in the real world or become part of routine healthcare. Whilst genome editing will never be a panacea for disease, its addition to the genetic medicine toolkit makes unavoidable and urgent the need to address ethical and practical considerations around its use that were previously matters for theoretical debate.

Making the most of genome editing

Internationally, genome editing techniques are being applied to explore and address a wide range of health challenges. Whilst this progress is exciting, structured and progressive thinking around appropriate and equitable use is still needed.

The UK is an international leader in innovation in cell and gene therapies, and to ensure patients receive the maximum benefit from these technologies we need new thinking around the interaction between these therapies and the healthcare system: potential infrastructure adaptations and development for delivery at scale, and suitable methods of regulation and reimbursement for developers of these expensive  personalised therapies.

The next policy briefing in our series on genome editing will outline the current state of genome editing therapies and discuss what comes next.

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