Self-complementary AAV vectors; advances and applications.
Numerous preclinical studies have demonstrated the efficacy of recombinant adeno-associated virus (rAAV) gene delivery vectors, and recent clinical trials have shown promising results. However, the efficiency of these vectors, in terms of the number of genome-containing particles required for transduction, is hindered by the need to convert the single-stranded DNA (ssDNA) genome into double-stranded DNA (dsDNA) prior to expression. This step can be entirely circumvented through the use of self-complementary vectors, which package an inverted repeat genome that can fold into dsDNA without the requirement for DNA synthesis or base-pairing between multiple vector genomes. The important trade-off for this efficiency is the loss of half the coding capacity of the vector, though small protein-coding genes (up to 55 kd), and any currently available RNA-based therapy, can be accommodated. The increases in efficiency gained with self-complementary AAV (scAAV) vectors have ranged from modest to stunning, depending on the tissue, cell type, and route of administration. Along with the construction and physical properties of self-complementary vectors, the basis of the varying responses in multiple tissues including liver, muscle, and central nervous system (CNS) will be explored in this review.
McCarty
Douglas M
DM
Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio 43205, USA. Douglas.McCarty@nationwidechildrens.org
D000818:Animals; D018076:DNA, Complementary; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral; D006801:Humans; D014018:Tissue Distribution; D014161:Transduction, Genetic
D018076:DNA, Complementary