Gene editing using large insertions

Abstract

While technologies for smaller gene edits, such as base editing, have already entered clinical trials, larger gene cargoes face different challenges, including low editing efficiencies, delivery vehicle size constraints, and possible immunogenicity. Programmable genome engineering systems using recombinases; transposases, including CRISPR-associated transposases (CASTs); genome writing systems; and retrotransposons promise different avenues for therapy, but each system has unique limitations. What are the most promising strategies to further develop these technologies, and which parameters need to be further improved to make them efficient and safe for therapy? We asked three experts in the field to share their thoughts on the challenges and opportunities.