CRISPR-mediated prenatal metabolic gene editing

December 13, 2018 0 By FM

A.C. Rossidis et al performed the first prenatal gene editing to prevent a lethal metabolic disorder in mice models, offering the potential to treat human congenital diseases before birth. The scientists used CRISPR-Cas9 and base editor 3 (BE3) gene editing tools in utero to reduce cholesterol levels in a wild-type mice. They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice that had been engineered with a mutation causing the lethal liver disease hereditary tyrosinemia type 1 (HT1). Adenovirus vectors were used for the delivery of CRISPR-Cas9 and BE3. Scientists observed a long-term postnatal persistence of edited cells in both models with reduced cholesterol levels and rescue of the lethal phenotype of HT1 following in utero gene targeting in respective mice models. Thus the research offers proof-of-concept for the prenatal use of a sophisticated, low-toxicity tool in efficient gene editing that helps point to a potential new therapeutic approach in treating selected congenital genetic disorders.

Nature Medicine, Volume 24, pages1513–1518 (2018) 8th October 2018