Motoi Kato, Shohei Ishikawa, Shen Qi, Du Zening, Takuya Katashima, Mitsuru Naito, Takao Numahata, Mutsumi Okazaki, Takamasa Sakai, and Masakazu Kurita
The adeno-associated virus (AAV) is a potent vector for in vivo gene transduction and local therapeutic applications of AAVs, such as for skin ulcers, are expected. Localization of gene expression is important for the safety and efficiency of genetic therapies. We hypothesized that gene expression could be localized by designing biomaterials using poly(ethylene glycol) (PEG) as a carrier. Here we show one of the designed PEG carriers effectively localized gene expression on the ulcer surface and reduced off-target effects in the deep skin layer and the liver, as a representative organ to assess distant off-target effects, using a mouse skin ulcer model. The dissolution dynamics resulted in localization of the AAV gene transduction. The designed PEG carrier may be useful for in vivo gene therapies using AAVs, especially for localized expression.
Communications Biology: https://www.nature.com/articles/s42003-023-04851-w