The promise of gene editing: so close and yet so perilously far.

Abstract

On the one hand, it is striking how the promise of genome editing is advancing. Regulatory restrictions have largely eased on genetically engineered crops that carry genome modifications that are similar to spontaneous mutations or those produced by conventional chemical or radiation-based methods (Van Vu et al., 2022). Plants produced by site-directed nuclease type 1 methods (SDN1), for which substitutions and indels are produced only by the action of the nuclease, have been deregulated in many countries. An exception are those countries within the European Union, where, despite being the third largest producer of genetically engineered crops behind China and the USA, SDN1 crops remain subject to the stringent regulations for genetically modified organisms (GMOs). Such stringent regulations are considered to have a dampening effect on agriculture innovation in the EU, and are perhaps similar to the dampening effect of long regulatory delays on the genetic engineering of livestock animals (Van Eenennaam et al., 2021). Since the first report of genetic engineering in livestock animals in 1985, only a single food animal has been commercialized. This is in part due to the USA Food and Drug Administration and their EU counterparts classifying any intentional altered genomic DNA in animals as an investigational new animal drug (INAD) that is not generally recognized as safe. However, there is a growing realization that the current EU policy towards SDN1 crops needs to be updated (Dima et al., 2022), giving hope to the wider use of these directed editing methods that can dramatically accelerate the production of new varieties compared to traditional breeding techniques. Interestingly, regulations have not hindered innovation in the application of genetic engineering to human health. In fact, this area has been a significant driver of technological advances. Recent publications and scientific meetings, such as the Keystone Symposium on Precision Genome Engineering and the American Society for Gene and Cell Therapy Annual Meeting, highlight the rapid advances in genome editing tools, driven in large part by a sense that new treatments for human disease enabled by these tools are just around the corner. Indeed, by some estimates there are over 100 products using genome editors now in clinical trial (CRISPR Medicine News), led by companies, such as CRISPR Therapeutics, Intellia Therapeutics, Sangamo Therapeutics, Editas Medicine, Precision Biosciences, Caribou Biosciences, Locus Biosciences, and many others. In the academic sector, Phase 1 of the NIH Somatic Cell Genome Editing Consortium (Saha et al., 2021), which had focused primarily on developing new editors and delivery methods, has led to a Phase 2 that is primarily focused on using these tools to OPEN ACCESS