Modified adeno-associated virus (AAV) vectors: A new generation of targeted gene therapy delivery systems.
Extract: Gene therapy in its simplest form is the deliberate transfer of therapeutic genes into a host cell. As a human gene therapy vector, Adeno-Associated Virus (AAV) is a promising delivery system. It is able to maintain stable gene expression in host cells, is efficient at gene delivery in vivo, and is non-pathogenic. However, one obstacle facing the advancement of AAV vectors is the natural tropism of the virus. The primary attachment receptor for AAV type-2 (AAV2) is heparan sulfate proteoglycan (HSPG). This receptor is widely expressed on many cell types, which creates a problem when delivering genes that promote cell death, as in anti-cancer gene therapy strategies. Conversely, cells that do not express HSPG cannot be transduced by AAV-2 based vectors. This can cause problems when gene delivery needs to be cell specific. As gene therapy moves forward, it will be imperative to develop AAV vectors that can be targeted to specific cellular receptors and therefore, specific cell types.
Sasser
A Kate
AK
Gene Therapy Center, Columbus Children's Research Institute, Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Bartlett
Jeffrey S
JS