Direct Gene Transfer into Nonhuman Primate Myofibers <i>In Vivo</i>

Jiao, Shoushu; Williams, Phillip; Berg, R; Hodgeman, Bradley A.; Liu, Lijian; Repetto, Gabriela M.; Wolff, Jon A.

doi:10.1089/hum.1992.3.1-21

Cited by 278 publications

(111 citation statements)

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“…Expression of the human apoE in injected muscle was detected by qualitative RT-PCR analysis for as long as 16 weeks after gene transfer. This result is in agreement with previous studies from Jiao et al 25 These authors demonstrated that the expression of naked plasmid DNA in the myofibers of nonhuman primate muscle persisted for at least 4 months.…”

Section: Discussionsupporting

confidence: 93%

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA

et al. 2000

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We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-deficient mice with 80 g of a plasmid vector (pCMV-E3) encoding the human apoE3 cDNA under the control of the CMV promoter-enhancer in both posterior legs. Local expression of the transgene was demonstrated throughout 16 weeks. Human apoE3 recombinant protein reached 0.6 ng/ml serum level. After i.m. injection of pCMV-E3 expression vector the mean serum cholesterol concentrations decreased from 439 ± 57 mg/dl to 253 ± 99 mg/dl (P Ͻ 0.05) 2 weeks after injection and persisted at a

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Section: Discussionsupporting

confidence: 93%

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA

et al. 2000

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“…However, comparing the mouse and rabbit models, NHPs more closely compare with human beings in the muscle structure, blood volume to mass ratio, viral receptors and immune response. 16 Here, we demonstrated rAAV1 and rAAV8 tropism for NHP WBCs after IM injection, although we did not assess whether transgene expression originates from infected WBCs. For Mac4, autoimmune anemia may have been facilitated by transduction of dendritic cells by the rAAV1 vector, which has been shown to be efficient at transducing this cell type.…”

Section: E+07mentioning

confidence: 71%

“…[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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“…The primary disadvantage of DNA vaccines has been that direct injection of plasmid DNA is inefficient in transfecting host cells, notably less efficient in primates compared with rodents [20]. Consequently, DNA vaccines are less potently immunogenic than viral vaccines.…”

Section: Introduction: Cancer Immunotherapy and Anti-tumor Vaccinesmentioning

confidence: 99%

DNA Vaccines for Prostate Cancer

McNeel

Becker

Johnson

et al. 2012

Current Cancer Therapy Reviews

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Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to be an effective means of immunization, capable of eliciting antigen-specific T cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine approaches in terms of simplicity, manufacturing, and possibly safety. The primary disadvantage is their poor transfection efficiency and subsequent lower immunogenicity relative to other genetic vaccine approaches. However, multiple preclinical models demonstrate anti-tumor efficacy, and many efforts are underway to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical trials using DNA vaccines as treatments for prostate cancer have begun, and to date have demonstrated safety and immunological effect. This review will focus on DNA vaccines as a specific means of antigen delivery, advantages and disadvantages of this type of immunization, previous experience in preclinical models and human trials specifically conducted for the treatment of prostate cancer, and future directions for the application of DNA vaccines to prostate cancer immunotherapy.

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Direct Gene Transfer into Nonhuman Primate Myofibers In Vivo

Cited by 278 publications

References 0 publications

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA

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

DNA Vaccines for Prostate Cancer

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