In utero CRISPR-mediated therapeutic editing of metabolic genes

In utero gene editing has the potential to prenatally treat genetic diseases that result in significant morbidity and mortality before or shortly after birth. We assessed the viral vector-mediated delivery of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated 9 (CRISPR-Cas9) or base editor 3 (BE3) in utero, seeking therapeutic modification of the Pcsk9 or Hpd gene in wild-type mice or the murine model of hereditary tyrosinemia type 1 (HT1), respectively.