(EN) The research team led by Prof. Feng Bo uncovers that carefully designed AAV-CRISPR achieved robust homology independent gene knock-in in live mice with low and safe AAV vector inputs, at the pre-selected target site in mAlb 3’UTR. This enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 -/-), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during 1-year observation.

The liver-specific therapeutic gene knock-in using low-dose AAV-CRISPR significantly reduced the risk of toxicity associated with high AAV inputs and resulted in subtle antibody response in neonates, lending important support to the development of AAV-CRISPR mediated somatic knock-in for treating inherited diseases.

The findings have been published in Nature Communications:
https://www.nature.com/articles/s41467-022-34898-y