Adeno-associated virus vectors: potential applications for cancer gene therapy

Abstract

Augmenting cancer treatment by protein and gene delivery continues to gain momentum based on success in animal models. The primary hurdle of fully exploiting the arsenal of molecular targets and therapeutic transgenes continues to be efficient delivery. Vectors based on adeno-associated virus (AAV) are of particular interest as they are capable of inducing transgene expression in a broad range of tissues for a relatively long time without stimulation of a cell-mediated immune response. Perhaps the most important attribute of AAV vectors is their safety profile in phase I clinical trials ranging from CF to Parkinson's disease. The utility of AAV vectors as a gene delivery agent in cancer therapy is showing promise in preclinical studies. In this review, we will focus on the basic biology of AAV as well as recent progress in the use of this vector in cancer gene therapy. Cancer Gene Therapy (2005) 12, 913-925.

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia

“…Recombinant AAV (rAAV) vectors can initiate long-term stable transgene expression in rodents and primates with rare host chromosome integration. 4 Currently, 12 naturally occurring serotypes of AAV and several primate isolates have been isolated and studied as gene delivery vehicles. 5,6 Clinical trials with rAAV2 vectors have been performed in hemophilia B (factor IX deficiency) patients via intramuscular injection or by targeting the liver.…”

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA

“…The ability of AAV to infect both dividing and nondividing cells, to transduce a broad range of tissues in vivo, and to direct long-term gene expression in these tissues made it an ideal vehicle for gene therapy. 25 AAV2 is the most widely studied AAV vector for gene transfer and has been applied in several clinical studies. 26 However, its application in liverdirected gene therapy is limited because of the poor transduction rate of hepatocytes 27 and existence of neutralizing antibodies in a large human population.…”

MIDGE/hNIS vaccination generates antigen‐associated CD8+IFN‐γ+ T cells and enhances protective antitumor immunity

“…6 Several vector systems have been used in clinical gene transfer trials to increase the efficiency of DNA delivery with retroviral and adenoviral vectors being most common. 7,8 Although the viral vectors can effectively and stably transduce the target cells, they are also associated with risks, such as recombination with wild-type viruses and the activation of protooncogenes. 9 A plasmid vector, which is comprised of double-stranded circular DNA, can avoid these risks.…”