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

Abstract

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

Advances in Genetic Editing of the Human Embryo

“…56 The tendency to patent a new technology and protect it in terms of intellectual property and the benefits arising from this patenting can delay access to a new technology for all people living in a less developed country, regardless of their age, thus ensuring different access and unequal distribution of the benefit of the emergence of these technologies. 57 Baylis et al showed that "A just and equitable society is one with less disparities and more justice. A predictable consequence of allowing (not, encouraging) individuals to genetically modify their children will be greater disparity and greater injustice-and not just because of limited access to genome-editing technology.…”

“…56 The tendency to patent a new technology and protect it in terms of intellectual property and the benefits arising from this patenting can delay access to a new technology for all people living in a less developed country, regardless of their age, thus ensuring different access and unequal distribution of the benefit of the emergence of these technologies. 57…”

Processes for regulating genetically modified and gene edited plants

“…The European Union, New Zealand, Norway, and Switzerland have to date consciously included crops and forages developed using New Breeding Technologies under the same legislation as all other GM crops. 4 , 7 , 32 , 194 , 285 This exposes contradictions. In Europe, importation of GM feed for animal is permitted but crops developed with GM technologies including those developed using New Breeding Technologies are regulated.…”

Directed evolution of hyperactive integrases for site specific insertion of transgenes

“…By overcoming the lack of efficiency of current methods, numerous applications would be accelerated, including (i) integration into genomes of cell lines used in industrial biotechnology for the production of pharmaceuticals and other proteins (6); (ii) introduction of desirable traits, such as disease resistance or enhanced nutritional content, into plant genomes (7,8); (iii) insertion of disease-related genes into genomes of animal models to study the mechanisms of various disorders and test therapeutic interventions (9); (iv) integration of genetic modules into synthetic genomes, allowing the creation of biological memory devices or genetic logic gates (10,11); (v) attachment of epitope tags or fusion proteins to study gene regulation and localization in situ or in vivo (12); and (vi) delivering therapeutic genes into the genomes of patients' cells (13)(14)(15). Tailoring a therapy to correct an individual's unique mutation is challenging, hence a full replacement of the coding sequence of a recessive gene is often needed for a single, common therapy to be effective (16). As treatments for increasingly complex diseases are undertaken, multi-gene insertions will be necessary requiring larger cargos beyond the limits of current virus-based approaches (17).…”