Widespread labeling and genomic editing of the fetal central nervous system by in utero CRISRP AAV9-PHP.eB administration

Efficient genetic manipulation in the developing central nervous system is critical to investigate mechanisms of neurodevelopmental disorders and develop promising therapeutics. Common approaches including transgenic mice and in utero electroporation (IUE), although powerful in many aspects, have their own limitations. In this study, we delivered vectors based on the AAV9.PHP.eB pseudo-type to the fetal mouse brain and achieved widespread and extensive transduction of neural cells. When AAV9.PHP.eB coding gRNA targeting PogZ or Depdc5 was delivered to Cas9 transgenic mice, widespread gene knockout was also achieved at the whole brain level. Our studies provide a useful platform for studying brain development and devising genetic intervention for severe developmental diseases.