Global status of gene edited animals for agricultural applications

Gene editing (GnEd) involves using a site-directed nuclease to introduce a double-strand break (DSB) at a targeted location in the genome. A literature search was performed on the use of GnEd in animals for agricultural applications. Data was extracted from 212 peer-reviewed articles that described the production of at least one living animal employing GnEd technologies for agricultural purposes. The most common GnEd system reported was CRISPR/Cas9, and the most frequent type of edit was the unguided insertion or deletion resulting from the repair of the targeted DSB leading to a knock-out (KO) mutation. Animal groups included in the reviewed papers were ruminants (cattle, sheep, goats, n=63); monogastrics (pigs and rabbits, n=60); avian (chicken, duck, quail, n=17); aquatic (many species, n=65), and insects (honeybee, silkworm, n=7). Yield (32%), followed by reproduction (21%) and disease resistance (17%) were the most commonly targeted traits. Over half of the reviewed papers had Chinese first-authorship. Several countries, including Argentina, Australia, Brazil, Colombia and Japan, have adopted a regulatory policy that considers KO mutations introduced following GnEd DSB repair as akin to natural genetic variation, and therefore treat these GnEd animals analogously to those produced using conventional breeding. This approach has resulted in a non-GMO determination for a small number of GnEd food animal applications, including three species of GnEd KO fast-growing fish, (red sea bream, olive flounder and tiger pufferfish in Japan), KO fish and cattle in Argentina and Brazil, and porcine reproductive and respiratory syndrome (PRRS) virus disease-resistant KO pigs in Colombia.