By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Data detailed on Herpesviridae Infections have been presented. According to news originating from Charlottesville, Virginia, by NewsRx correspondents, research stated, "Targeting therapeutic gene expression to the skeletal muscle following intravenous (IV) administration is an attractive strategy for treating peripheral arterial disease (PAD), except that vector access to the ischemic limb could be a limiting factor. As adeno-associated virus serotype 9 (AAV-9) transduces skeletal muscle at high efficiency following systemic delivery, we employed AAV-9 vectors bearing luciferase or enhanced green fluorescent protein (eGFP) reporter genes to test the hypothesis that increased desialylation of cell-surface glycans secondary to hindlimb ischemia (HLI) might help offset the reduction in tissue perfusion that occurs in mouse models of PAD."
Our news journalists obtained a quote from the research from the University of Virginia, "The utility of the creatine kinase-based (CK6) promoter for restricting gene expression to the skeletal muscle was also examined by comparing it with the cytomegalovirus (CMV) promoter after systemic administration following surgically induced HLI. Despite reduced blood flow to the ischemic limbs, CK6 promoter-driven luciferase activities in the ischemic gastrocnemius (GA) muscles were similar to 34-, similar to 28-and similar to 150-fold higher than in the fully perfused contralateral GA, heart and liver, respectively, 10 days after IV administration. Furthermore, luciferase activity from the CK6 promoter in the ischemic GA muscles was similar to twofold higher than with CMV, while in the liver CK6-driven activity was similar to 42-fold lower than with CMV, demonstrating that the specificity of ischemic skeletal muscle transduction can be further improved with the muscle-specific promoters. Studies with Evans blue dye and fluorescently labeled lectins revealed that vascular permeability and desialylation of the cell-surface glycans were increased in the ischemic hindlimbs. Furthermore, AAV9/CK6/Luc vector genome copy numbers were similar to sixfold higher in the ischemic muscle compared with the non-ischemic muscle in the HLI model, whereas this trend was reversed when the same genome was packaged in the AAV-1 capsid (which binds sialylated, as opposed to desialylated glycans), further underscoring the importance of desialylation in the ischemic enhancement of transduction displayed by AAV-9. Taken together, these findings suggest two complementary mechanisms contributing to the preferential transduction of ischemic muscle by AAV-9: increased vascular permeability and desialylation."
According to the news editors, the research concluded: "Ischemic muscle is preferentially targeted following systemic administration of AAV-9 in a mouse model of HLI. Unmasking of the primary AAV-9 receptor as a result of ischemia may contribute importantly to this effect."
For more information on this research see: Adeno-associated virus serotype 9 efficiently targets ischemic skeletal muscle following systemic delivery. Gene Therapy, 2013;20(9):930-938. Gene Therapy can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St, London N1 9XW, England. (Nature Publishing Group - www.nature.com/; Gene Therapy - www.nature.com/gt/)
The news correspondents report that additional information may be obtained from A.B. Katwal, University of Virginia, Dept. of Radiol, Charlottesville, VA 22903, United States. Additional authors for this research include P.R. Konkalmatt, B.A. Piras, S. Hazarika, S.S. Li, R.J. Lye, J.M. Sanders, E.A. Ferrante, Z. Yan, B.H. Annex and B.A. French (see also Herpesviridae Infections).
Keywords for this news article include: CMV, Biotechnology, Viruses, Virginia, Genetics, Virology, Luciferases, Gene Therapy, United States, Bioengineering, Charlottesville, Oxidoreductases, Luminescent Proteins, Enzymes and Coenzymes, Adeno-Associated Virus, Herpesviridae Infections, North and Central America, Cytomegalovirus Infections
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