Yoon, Y. et al. Nat. Commun. 9, 412 (2018).

Genetic manipulations in mice have become easier with the CRISPR-Cas9 system; however, the delivery of the necessary components into embryos, as well as the embryo handling, remains challenging. Yoon et al. now show that nucleic acid delivery methods such as microinjection and electroporation can be replaced by transduction of pre-implantation embryos with recombinant adeno-associated viruses (rAAVs). Many AAV serotypes can successfully transduce embryos, but serotype 6 proved to be the most efficient. When targeting the tyrosinase gene (involved in eye pigmentation and coat color), the researchers obtained chimeras with up to 100% efficiency, with most of the animals in the experiment developing into albinos. The researchers further simplified the genome-editing process in mice by introducing the rAAVs into oviducts of pregnant females, where embryos could be transduced in situ. Thus, this approach makes genome editing possible within pregnant animals, which avoids the need for embryo handling outside of the female reproductive tract.