The use of genome-editing techniques in medical therapies has proved to be a promising development in the treatment of certain diseases, such as cancer, HIV and rare diseases, by genetically altering specific types of cells. Compared to other techniques used to insert, delete or replace DNA in the genome of an organism, CRISPR/Cas9 is much quicker, easier to use and less costly, may be more precise in its application, and can also be used to edit multiple genes simultaneously. The technique therefore has the potential to be a true “game-changer” in medicine with profound beneficial effects on human health. However, the enthusiasm for the opportunities of this promising technology should be accompanied by adequate regulatory oversight to guarantee the safety of products and applications that use this technology.
The first clinical trial using CRISPR-edited immune cells began in patients with lung cancer in China in 2016. Earlier this year, FDA’s Recombinant DNA Advisory Committee did not find any objections to the first clinical protocol to use CRISPR/Cas9-mediated gene editing, and the first US clinical trial is expected to start shortly. Several more clinical trials have since been approved and started in China, including one which proposes to perform gene editing in vivo – i.e. directly within the body of live patients (as opposed to ex vivo, e.g. using cells extracted from donors).
Most recently, in August 2017, a team of US-based scientists at Oregon Health and Science University published a paper describing the successful use of CRISPR/Cas9 to fix a disease-causing DNA error in dozens of early-stage human embryos, which, according to biologist Shoukrat Mitalipov, brings us “much closer to clinical applications.” Clinical use of this work would mean actually implanting some of these embryos with the goal of children being born that possess genes which have been artificially edited using CRISPR technology and would be capable of passing those edited genes to their offspring. These developments are exciting for patients and their loved ones, but in equal measure represent a challenge to existing regulatory structures and society at large. At any rate, with the pace of development in the CRISPR field around the world, clinical trials involving CRISPR in the EU may not be far away.
Regulators in the EU and abroad will need to stay abreast of this new (r)evolution in genome-editing technologies. In this respect, different groups established within the European Commission, including the European Group on Ethics in Science and New Technologies, have emphasised the “great potential [of the CRISPR/Cas9 genome-editing technology] due to its many advantages to previous methods” and acknowledged that the CRISPR/Cas9 system challenges the international regulatory landscape for the modification of human cells in the near to medium term.
While no specific regulatory guidance has been issued to date, the European Medicines Agency (EMA) has started to lay the groundwork for the regulatory implications to come, by launching a public consultation on the revision of its Guideline on medicinal products containing genetically modified cells on 20 July 2017. The EMA specifically recognises that the current 2012 guideline focuses on genetic modifications by traditional methods (based on the use of vectors carrying recombinant nucleic acids), but that the introduction of the CRISPR/Cas9 system has rapidly increased the use of genome-editing technologies to genetically modify cells ex vivo for clinical applications, and aims to take these aspects into consideration in its revised draft guideline, which is expected by March 2018.
This is an exciting time for research and development wherein the use of CRISPR in medicine may lead to rapid and significant progress for human health. The regulation of the developments triggered by this new technology is important to ensure that, on the one hand, appropriate quality and safety standards are adhered to, by way of evaluating and mitigating potential risks and, on the other, a clear and certain regulatory environment is created to encourage researchers to explore fully the potential of this technology within the ethical bounds society deems appropriate. It appears that the regulation of gene and cell therapies under the EU ATMP Regulation – possibly with some regulatory modifications and the adoption of adequate scientific guidelines – could also govern revolutionary gene-editing techniques such as CRISPR/Cas9, and is therefore the legal instrument to watch as CRISPR continues to conquer the world of medicine.
For more information on the framework for gene-edited products in the European Union and how this could govern CRISPR/Cas9, please read our paper available on A&O’s website here.