GFP Adeno-Associated Virus ( AAV-Kera3 )

Human skin equivalents are indicated for conditions with poor healing, such as chronic wounds or extensive skin burns. While a pro-inflammatory microenvironment is an important barrier to initial engraftment, poor perfusion can hinder the long-term survival of skin equivalents. Genetic modification of keratinocytes is an attractive strategy to address these issues. In addition, skin gene therapy can be applied to a variety of inherited skin blistering or barrier diseases, for which there are currently no treatments. To advance skin gene therapy toward clinical application, efficient and safe delivery vehicles are required.

The AAV-Kera3 capsid was engineered from AAV serotype 2 (AAV2), a widely studied viral vector known for its safety and low immunogenicity. A key feature of the AAV-Kera3 variant is the strategic insertion of a peptide sequence (RGDQQSL) at position 587 of the capsid protein. This peptide insertion is designed to exploit the natural affinity of keratinocytes for certain extracellular matrix components, thereby enhancing the ability of the virus to selectively bind and transduce these cells. AAV-Kera3 can be used for genetic manipulation of primary human keratinocytes (HK), and they can not only transduce HK seeded in monolayers but also show tropism for keratinocytes in the presence of feeder cells.