Recent developments in recombinant AAV-mediated gene therapy for lung diseases.
Recent studies have shed light on a number of important obstacles to safe and effective gene transfer to the respiratory tract with recombinant AAV vectors. Among these are blocks at the level of receptor binding and internalizations, evasion of proteasomal degradation, inefficiency of nuclear entry, and nuclear factors that inhibit the conversion of rAAV genomes into active double-stranded DNA form. Other important issues have been the size constraints of the vector, the lack of retention of episomal forms of the vector genome, and immune responses which may limit the efficiency of repeated doses of rAAV. Each of these potential obstacles has been addressed with new vector designs. In addition, the availability of an abundance of novel rAAV serotypes, each with its own receptor tropism, has expanded the range of possibilities for long-term success of gene therapy in the respiratory tract.
Powell Gene Therapy Center, Genetics Institute, Department of Pediatrics, University of Florida, 1600 SW Archer Rd., Box 100296, Gainesville, FL 32610-0296, USA. flotttr@peds.ufl.edu
Terence R
TR
Flotte
D000818:Animals; D036022:Capsid Proteins / Q000235:genetics; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008171:Lung Diseases / Q000235:genetics / Q000628:therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011995:Recombination, Genetic; D012703:Serotyping
D036022:Capsid Proteins; D011505:Protein-Tyrosine Kinases