Gene therapy progress and prospects: Recombinant adeno-associated virus (rAAV) vectors

Progress Many new AAV serotypes have been discovered Structural biology of AAV opens the door to new vector designs Receptor-targeted capsid mutants and alternative serotypes broaden the host range for rAAV-mediated gene transfer Postentry limitations to rAAV-mediated gene transfer have been identified, including proteasome-mediated vector degradation and limitations on transcriptional activation New data on the mechanisms of rAAV persistence help define potential risks and benefits of rAAV-mediated transduction Progress in rAAV production technology makes new applications feasible Clinical trials utilizing rAAV are expanded Barriers to rAAV-mediated gene transfer in the clinical setting are identified Barriers to repeated dosing of rAAV Prospects Use of small molecules to overcome intracellular barriers to rAAV transduction Clinical applications based on achieving sustained secretion of extracellular transgene products Gene modification approaches to regenerative medicine.