Gene transfer in skeletal and cardiac muscle using recombinant adeno-associated virus
Gene Therapy Center; Department of Microbiology and Physiological Systems; Department of Pediatrics
Medical Subject Headings
Dependovirus; Genetic Vectors; Genetic Therapy; Gene Transfer Techniques; Muscle, Skeletal; Myocardium
Genetics and Genomics | Microbiology | Molecular Genetics
Adeno-associated virus (AAV) is a DNA virus with a small ( approximately 4.7 kb) single-stranded genome. It is a naturally replication-defective parvovirus of the dependovirus group. Recombinant AAV (rAAV), for use as a gene transfer vector, is created by replacing the viral rep and cap genes with the transgene of interest along with promoter and polyadenylation sequences. Only the viral inverted terminal repeats (ITRs) are required in cis for replication and packaging during production. The ITRs are also necessary and sufficient for vector genome processing and persistence during transduction. The tissue tropism of the rAAV vector is determined by the AAV capsid. In this unit we will discuss several methods to deliver rAAV in order to transduce cardiac and/or skeletal muscle, including intravenous delivery, intramuscular delivery, isolated limb infusion, intrapericardial injection in neonatal mice, and left ventricular wall injection in adult rats.
Gruntman, Alisha M.; Bish, Lawrence T.; Mueller, Christian; Sweeney, H. Lee; Flotte, Terence R.; and Gao, Guangping, "Gene transfer in skeletal and cardiac muscle using recombinant adeno-associated virus" (2013). University of Massachusetts Medical School Faculty Publications. 191.