AAV-F demonstrated a 119-fold increased GFP fluorescence coverage in the murine brain compared to the parental AAV9 vector following systemic administration.
Does the novel AAV-F capsid improve CNS transgene expression compared to parental AAV9 in mice?
AAV-F, a novel AAV capsid identified via the iTransduce library method, mediates highly efficient and robust transgene expression in the murine CNS after systemic delivery.
Effect estimate: 119-fold increase
p-value: p=<0.0001
Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F.
Hanlon et al. (Wed,) conducted a other in CNS transgene expression. AAV-F vs. AAV9 was evaluated on GFP fluorescence coverage in the brain (119-fold increase, p=<0.0001). AAV-F demonstrated a 119-fold increased GFP fluorescence coverage in the murine brain compared to the parental AAV9 vector following systemic administration.