Biology of Adeno-associated Virus

Berns, Kenneth I.; Giraud, Catherine

doi:10.1007/978-3-642-80207-2_1

Cited by 198 publications

(178 citation statements)

References 116 publications

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“…1,2 AAVs share varying degrees of similarities to autonomous parvoviruses including Canine parvovirus (CPV), Feline parvovirus (FPV), and minute virus of mice. 3 As such, comparative biology of these related parvoviruses has been useful to the study of AAVs.…”

Section: Introductionmentioning

confidence: 99%

Intracellular trafficking of adeno-associated viral vectors

et al. 2005

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Adeno-associated virus (AAV) has attracted considerable interest as a gene therapy vector over the past decade. In all, 85% of the current 2052 PubMed references on AAV (as of December 2004) have been published in the last 10 years. As researchers have moved forward with using this vector system for gene delivery, an increased appreciation for the complexities of AAV biology has emerged. The biology of recombinant AAV (rAAV) transduction has demonstrated considerable diversity in different cell types and target tissues. This review will summarize the current understanding of events that control rAAV transduction following receptor binding and leading to nuclear uptake. These stages are broadly classified as intracellular trafficking and have been found to be a major rate-limiting step in rAAV transduction for many cell types. Advances in understanding this area of rAAV biology will help to improve the efficacy of this vector system for the treatment of inherited and acquired diseases. Gene Therapy (2005) 12, 873-880.

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Section: Introductionmentioning

confidence: 99%

Intracellular trafficking of adeno-associated viral vectors

et al. 2005

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“…1 Given their safety and low toxicity, ability to infect nondividing cells and long-term gene expression when used as a vector for gene delivery, AAV has become a favored candidate for gene therapy. 2,3 Several clinical trials utilizing AAV for the treatment of cystic fibrosis, hemophilia, prostate cancer and muscular dystrophy are underway, with early evidence of human clotting factor IX production in hemophilia B patients.…”

Section: Introductionmentioning

confidence: 99%

Immunity to adeno-associated virus serotype 2 delivered transgenes imparted by genetic predisposition to autoimmunity

et al. 2004

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“…1,2 The AAV genome is a single-stranded DNA, which is transcriptionally inactive. 3,4 Thus, failure to undergo viral second-strand synthesis remains a predominant rate-limiting step in the observed low efficiency of singlestranded AAV (ssAAV) vector-mediated transgene expression both in vitro and in vivo. [5][6][7][8][9][10][11][12][13][14] The use of selfcomplementary AAV (scAAV) vectors that bypass the requirement for viral second-strand DNA synthesis can circumvent this problem.…”

mentioning

confidence: 99%

Strategies for improving the transduction efficiency of single-stranded adeno-associated virus vectors in vitro and in vivo

Jayandharan

Zhong

et al. 2008

Gene Ther

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Recombinant vectors based on adeno-associated virus type 2 (AAV) target the liver efficiently, but the transgene expression is limited to B5% of murine hepatocytes. Viral second-strand DNA synthesis continues to be a rate-limiting step for efficient transduction by the single-stranded AAV (ssAAV) vectors. This is due, in part, to the presence of a cellular chaperone (FK506-binding) protein, FKBP52, phosphorylated forms of which interact with the D-sequence in the inverted terminal repeats of AAV2 genome and inhibit the viral second-strand DNA synthesis. Our previous studies have documented that dephosphorylation of FKBP52 at tyrosine residues by the cellular T-cell protein tyrosine phosphatase (TC-PTP), and at serine/threonine residues by protein phosphatase 5 (PP5) enhances viral secondstrand DNA synthesis and consequently, the transgene expression. We have also reported that coinfection with a self-complementary AAV (scAAV)-TC-PTP vector results in up to sixfold increase in the transduction efficiency of conventional ssAAV2 vectors in primary murine hepatocytes in vivo. We reasoned that coinfection with scAAV-TC-PTP and scAAV-PP5 vectors may lead to a further increase in the transduction efficiency of ssAAV2 vectors. We demonstrate here that this strategy does indeed lead to B16-fold increase in the transduction efficiency of conventional ssAAV vectors in primary murine hepatocytes in vivo following tail-vein injections. Neither scAAV2-TC-PTP nor scAAV2-PP5 vectors alone or together had any adverse effect on the hepatocytes. Thus, this coinfection strategy may be useful for achieving expression from recombinant ssAAV2 vectors containing larger genes, such as coagulation factor VIII, which exceed the packaging capacity of scAAV vectors, for the potential gene therapy of hemophilia A.

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Biology of Adeno-associated Virus

Cited by 198 publications

References 116 publications

Intracellular trafficking of adeno-associated viral vectors

Intracellular trafficking of adeno-associated viral vectors

Immunity to adeno-associated virus serotype 2 delivered transgenes imparted by genetic predisposition to autoimmunity

Strategies for improving the transduction efficiency of single-stranded adeno-associated virus vectors in vitro and in vivo

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