Embryo and Fetal Gene Editing: Technical Challenges and Progress towards Clinical Applications

Gene modification therapies (GMT) are slowly but steadily making progress towards clinical application. As the majority of rare diseases have an identified genetic cause, and as rare diseases collectively affect 5% of the global population, it is increasingly important to devise gene correction strategies to address the root causes of the most devastating of these diseases, and to provide access to these novel therapies to the most affected populations. The main barriers to providing greater access to GMT continue to be the prohibitive cost of developing these novel drugs at clinically-relevant doses, subtherapeutic effects and toxicity related to the specific agents or high doses required. In vivo strategy and treating younger patients at an earlier course of their disease could lower these barriers. Though currently regarded as niche specialties, prenatal and preconception GMT offer a robust solution to some of these barriers. Indeed, treating either the fetus or embryo benefits from economy of scale, targeting pre-pathological tissues in the fetus prior to full pathogenesis, or increasing the likelihood of complete tissue targeting by correcting pluripotent embryonic cells. Here we review advances in embryo and fetal GMT and discuss requirements for clinical application.