Recombinant adeno-associated virus for muscle directed gene therapy

Fisher, Krishna J.; Jooss, Karin; Alston, J. M.; Yang, Yiping; Haecker, Sarah Ehlen; High, Katherine A.; Pathak, Ravindra K.; Raper, Steven E.; Wilson, James M.

doi:10.1038/nm0397-306

Cited by 610 publications

(460 citation statements)

References 32 publications

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“…18,41 Skeletal muscle in particular has been used successfully for long -term expression of transgenes by rAAV. 21,30,42,43 When this approach was taken in the present investigation, it was observed that a single intramuscular injection of the rAAVHuEndo vector could lead to elevated serum endostatin levels by 4 weeks after injection (Fig 7 ). The endostatin levels reached a plateau value by 6 to 8 weeks (Fig 7) and were maintained as long as 4 months after injection.…”

Section: Discussionmentioning

confidence: 79%

Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

et al. 2002

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A variety of approaches has demonstrated that interfering with tumor -induced angiogenesis may be an effective strategy in cancer therapy. However, it is likely that to be most effective such strategies will require extended suppression of the angiogenic process. Gene therapy offers a possible approach to achieve sustained release of a therapeutically potent transferred gene product. In the present study the angiogenesis inhibitor endostatin was expressed through a recombinant adeno -associated viral ( rAAV ) vector and shown to be biologically active in vitro and in vivo. Intramuscular injection of rAAV -HuEndo ( 1Â10 9 i.u. ) led to a sustained serum endostatin level of $35 -40 ng / mL. This endostatin level was sufficient to inhibit tumor cell -induced angiogenesis and to suppress both the initiation and subsequent growth of a human colorectal cancer model.

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Section: Discussionmentioning

confidence: 79%

Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

et al. 2002

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“…[5][6][7][8][9] Intramuscular (IM) injection is a convenient method owing to physical accessibility, mass of the tissue and access to the vasculature. [10][11][12] Moreover, recombinant adeno-associated viral (rAAV) vectors and naked plasmid are two different gene transfer systems used for IM delivery in animal models [13][14][15][16][17] and in humans. 18,19 Recently, regional vascular infusion of a vector to achieve skeletal muscle transduction has been reported for plasmid DNA (pDNA) 20,21 and for rAAV vectors.…”

Section: Introductionmentioning

confidence: 99%

Longevity of rAAV vector and plasmid DNA in blood after intramuscular injection in nonhuman primates: implications for gene doping

Guiner

Gernoux

et al. 2011

Gene Ther

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Legitimate uses of gene transfer technology can benefit from sensitive detection methods to determine vector biodistribution in pre-clinical studies and in human clinical trials, and similar methods can detect illegitimate gene transfer to provide sports-governing bodies with the ability to maintain fairness. Real-time PCR assays were developed to detect a performance-enhancing transgene (erythropoietin, EPO) and backbone sequences in the presence of endogenous cellular sequences. In addition to developing real-time PCR assays, the steps involved in DNA extraction, storage and transport were investigated. By real-time PCR, the vector transgene is distinguishable from the genomic DNA sequence because of the absence of introns, and the vector backbone can be identified by heterologous gene expression control elements. After performance of the assays was optimized, cynomolgus macaques received a single dose by intramuscular (IM) injection of plasmid DNA, a recombinant adeno-associated viral vector serotype 1 (rAAV1) or a rAAV8 vector expressing cynomolgus macaque EPO. Macaques received a high plasmid dose intended to achieve a significant, but not life-threatening, increase in hematocrit. rAAV vectors were used at low doses to achieve a small increase in hematocrit and to determine the limit of sensitivity for detecting rAAV sequences by single-step PCR. DNA extracted from white blood cells (WBCs) was tested to determine whether WBCs can be collaterally transfected by plasmid or transduced by rAAV vectors in this context, and can be used as a surrogate marker for gene doping. We demonstrate that IM injection of a conventional plasmid and rAAV vectors results in the presence of DNA that can be detected at high levels in blood before rapid elimination, and that rAAV genomes can persist for several months in WBCs.

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“…In a number of pilot studies the lacZ gene delivered by an AAV vector has been shown to make active ␤-galactosidase in cultured cells and animal tissues. [18][19][20][21] In treated muscle of immunocompetent mice, this expression was shown to persist for 1.5 years. 19 Potentially therapeutic proteins that have been shown to be delivered and expressed by AAV vectors include erythropoietin, 20 cystic fibrosis transmembrane conductance regulator, 22 blood coagulation factor IX, 23,24 and GUS.…”

Section: Introductionmentioning

confidence: 99%

“…19 Potentially therapeutic proteins that have been shown to be delivered and expressed by AAV vectors include erythropoietin, 20 cystic fibrosis transmembrane conductance regulator, 22 blood coagulation factor IX, 23,24 and GUS. 21 In none of these cases, however, were experiments designed to show that the AAV-mediated gene therapy actually affected the long-term course of a disease. Results presented here show that MPS VII mice treated with an AAV vector containing mouse GUS cDNA (AAV-GUS) acquire the ability to make GUS enzyme for an extended period of time.…”

Section: Introductionmentioning

confidence: 99%

Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus

Watson¹,

Sayles²,

Chen³

et al. 1998

Gene Ther

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Mucopolysaccharidosis type VII (MPS VII) is a lysosomalproduced low GUS activity in several tissues. This latter storage disease caused by a genetic deficiency of ␤-glucutreatment of MPS VII mice reduced glycosaminoglycan ronidase (GUS). We used a recombinant adeno-associalevels in the liver to normal and reduced storage granules ted virus vector (AAV-GUS) to deliver GUS cDNA to MPS dramatically. We show that a single administration of VII mice. The route of vector administration had a dramatic AAV-GUS can provide sustained expression of GUS in a effect on the extent and distribution of GUS activity. Intravariety of cell types and is sufficient to reverse the disease muscular injection of AAV-GUS resulted in high, localized phenotype at least in the liver. production of GUS, while intravenous administration

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Recombinant adeno-associated virus for muscle directed gene therapy

Cited by 610 publications

References 32 publications

Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

Longevity of rAAV vector and plasmid DNA in blood after intramuscular injection in nonhuman primates: implications for gene doping

Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus

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