Local delivery of adeno‐associated viral vectors with electrospun gelatin nanofiber mats

Abstract

Adeno‐associated viral (AAV) vectors play a significant role in gene therapy, yet the typical delivery methods, like systemic and local AAV injections, often lead to unintended off‐target distribution and tissue damage due to injection. In this study, we propose a localized delivery approach for AAV vectors utilizing electrospun gelatin nanofiber mats, which are cross‐linked with glutaraldehyde. The AAV vectors, which encoded a green fluorescent protein (GFP), were loaded onto the mats by immersing them in a solution containing the vectors. The amount of AAV vector loaded onto the mats increased as the vector concentration in the solution increased. The loaded AAV vector was steadily released into the cell culture medium over 3 days. The mats incubated for 3 days also showed the ability to transduce into the cells cultured on them. We evaluated the effectiveness of this delivery system by attaching the mats to mouse livers. GFP expression was visible on the surface of the liver beneath the attached mats, but not in areas in direct contact with the mats. These findings suggest that the attachment of AAV vector‐loaded electrospun gelatin nanofiber mats to a target site present a promising solution for localized gene delivery while reducing off‐target distribution.

Transduction and Genome Editing of the Heart with Adeno-Associated Viral Vectors Loaded onto Electrospun Polydioxanone Nonwoven Fabrics

“…We reported a similar result for electrospun gelatin fabrics applied to mouse liver [23]. As reported in various studies, electrospun fibers have been shown to be effective for the local delivery of vectors [16,[21][22][23]30]. However, it is impossible to completely prevent their off-target distribution, and not only with PDO fibers, due to the diffusion of the released vectors through the bloodstream and body fluids.…”

“…The large surface areas of the fabrics allow for the efficient loading and retention of genes, and the utility of electrospun nonwoven fabrics as a substrate for gene delivery has been demonstrated [16,[21][22][23].…”

“…These fine-fiber fabrics, with their extensive large surface areas and extracellular matrix-like structure, offer significant advantages for biomedical applications [20]. The large surface areas of the fabrics allow for the efficient loading and retention of genes, and the utility of electrospun nonwoven fabrics as a substrate for gene delivery has been demonstrated [16,[21][22][23].…”