Mohammadsharif Tabebordbar

Highlights • A family of muscle-tropic capsids identified by directed evolution in mice and primates • MyoAAV transduction is dependent on integrin heterodimers in mouse and human cells • MyoAAV administration at low dose results in therapeutic efficacy in disease models • Systemically administrated MyoAAV transduces primate muscles highly efficiently Summary Replacing or editing disease-causing mutations holds great promise for treating many human diseases.

Highlights • Multiple AAV serotypes transduce tissue stem cells via systemic or local delivery • AAV-delivered Cre recombinase modifies stem cells in multiple anatomical niches • In vivo AAV transduction does not require stem cell isolation or transplantation • AAV-transduced stem cells retain differentiation and engraftment capacities Summary In vivo delivery of genome-modifying enzymes holds significant promise for therapeutic applications and functional genetic screening.

Much of the controversy surrounding the gene-editing technology called CRISPR/Cas9 centers on the ethics of germline editing of human embryos to correct disease-causing mutations. For certain disorders such as muscular dystrophy, it may be possible to achieve therapeutic benefit by editing the faulty gene in somatic cells. In proof-of-concept studies, Long et al., Nelson et al., and Tabebordbar et al.