It’s All in the Delivery: Improving AAV Transfection Efficiency with Exosomes

Conversely, exo-AAVs might be useful for expressing genes to address dysfunction in supporting cells, as previously shown.9 Thus, accomplishing specific delivery to a sub-compartment of the inner ear (cochlea versus vestibular) or expression within a particular cell type is an important next step toward clinical application of gene therapy for treating inner-ear disease and may be influenced by specific regulatory elements that guide expression. [...]the data reported in the paper were obtained in neonatal mice in which inner ears are immature, and it is unclear how relevant the results will be for more mature ears. Interestingly, other studies that have attempted viral-vector-mediated rescue of genetic deafness in mouse mutants have also reported positive outcomes only in developing ears.3,4,9 Exo-AAV1 as a delivery vehicle for gene replacement is relevant for treating loss-of-function alleles; however, it may be less useful for gain of function or missense sequence variants that result in novel protein activities, because these altered proteins may not respond to gene replacement strategies.