15 June 2016
Genome editing - hot or not? View the full infographic here
CRISPR-Cas9 is the genome editing technology that everyone is talking about, thanks to its relative low cost, speed and perhaps most of all ease of use. Together these elements are effectively democratising gene editing, taking the technology out of the hands of the few, highly specialist laboratories and putting it into the hands of the many. This very accessibility is, however, creating concern that the research is moving too quickly, and doom-laden headlines about gene edited embryos and designer babies have been dominating the debate.
Anxiety about editing the human germline arguably risks diverting attention from the applications where CRISPR-Cas9 is already in use or has great potential to help the battle against disease with considerably less controversy: in scientific research and in certain areas of medicine.
The CRISPR-Cas9 technique uses two pieces of biological machinery: a guide RNA, which is created in the laboratory and binds to the genome section of interest, and the Cas9 enzyme, which cuts the target DNA sequence where the guide RNA has bound. The cell's repair mechanisms then fix the break, either by connecting the loose ends (inactivating the gene in the process), or using a DNA template provided by researchers to fix the break with an altered version of the gene. In this way gene sequences can be inactivated or replaced, as required.
Genome editing is already being used to develop cell and animal models for disease research and to study basic biology. And it is proving its usefulness in speeding up research - with genome editing, mouse models of disease can be generated in 3-4 months, rather than the 1-2 years it usually takes.
Current clinical uses for genome editing fall into two broad categories:
i) Treatments where a patient's cells or donor cells are removed, edited in the laboratory (outside the body) and then transplanted into the patient to treat a disease
ii) Treatments where the genome editing machinery is delivered to the affected tissue or organ and corrects the genetic fault causing a disease inside the body.
The first approach is being pursued to treat blood or immunological disorders. One patient with acute lymphoblastic leukaemia has already been successfully treated using gene edited T-cells from a donor and a clinical trial is planned.
The second approach is much more challenging, since it is difficult to ensure accurate delivery of the editing machinery and that clinically meaningful levels of editing have taken place. Nevertheless, trials in humans are planned in the US using gene editing technology to correct the faulty clotting factor IX gene in the liver, which is responsible for haemophilia B. In another group of studies, researchers have already used viral vectors to deliver gene editing machinery to the muscles of a mouse model of Duchenne muscular dystrophy, corrected the defective dystrophin gene and shown an improvement in symptoms.
The far more controversial application of the technique for germline editing of human embryos has to date only been used in a research context. However, there is concern that it could easily be taken further in countries with little or no regulatory oversight. In the UK, the Human Fertilisation and Embryology Authority has given permission for a researcher to use gene editing technologies to study human embryo development, but current legal restrictions still apply: it is illegal to use these embryos to generate a pregnancy, and the embryos must be destroyed after 14 days.
Given the speed with which genome editing technologies are progressing, what are the most pressing challenges?
The complexity of genome editing technologies and the degree of personalisation of some therapies, for example those that use a patient's own cells, are likely to challenge current regulations. There are several organisations with an interest in the technology and its applications, and to avoid promising therapies disappearing into a regulatory tangle, a centralised and coordinated approach will be needed to streamline the regulatory process. The question is, whether or not the clinical trials framework is capable of accommodating the types of studies needed to assess the safety and efficacy of these new, highly personalised therapies?
Some researchers are concerned that research is moving so quickly that the community does not have enough time to thoroughly discuss the ethical, legal, social and safety issues surrounding the use of genome editing technology. The scientific community has already begun to self-regulate in terms of germline editing, organising discussion meetings and issuing moratoria, which is a promising development. For the moment, a collaborative approach to understanding the biology of the CRISPR-Cas9 technique will be vital to promote the development of standardised techniques and procedures, and to collect as much data as possible on its safety and efficacy.
While CRISPR-Cas9 genome editing has been hailed as the technique that is going to revolutionise genomic medicine at record speed, it’s time to apply the reality brakes. There is still an enormous amount of work to be done to understand even the basic 'nuts and bolts' of the technique and many hurdles to overcome. Hopes that CRISPR-Cas9 based therapies will be widely available in the next couple of years are wildly optimistic - it will be quite a while before patients with serious illnesses can expect to be offered these therapies as routine.
Read more PHG Foundation perspectives on what's hot (or not) in healthcare futures.