PRJNA417970
A recombinant AAV-compatible miRNA scaffold for effective and precise gene silencing
Efficiency and specificity are known issues for recombinant adeno-associated virus (rAAV)-mediated RNAi therapeutics. Recently, short DNA hairpin-induced truncated rAAV genomes raised further concerns for its clinical transition. By embedding the guide strand of silencing RNAs into an artificial miRNA scaffold, based upon mouse primary miRNA-33, we improved the genomic integrity of rAAV vectors, achieving a ten-fold reduction in off-targeting while maintaining effective gene knockdown in cultured cells and mice