By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Investigators publish new report on Biotechnology. According to news reporting out of Chapel Hill, North Carolina, by NewsRx editors, research stated, "A drawback of gene therapy using adeno-associated virus (AAV) is the DNA packaging restriction of the viral capsid (
Our news journalists obtained a quote from the research from the University of North Carolina, "Herein, AAV production using an oversized reporter (6.2kb) resulted in chloroform and DNase-resistant particles harboring distinct 'fragment' AAV (fAAV) genomes (5.0, 2.4, and 1.6kb). Fractionation experiments determined that only the larger 'fragments' mediated transduction in vitro, and relatively efficient transduction was also demonstrated in the muscle, the eye, and the liver. In contrast with concatemerization-dependent large-gene delivery by split AAV, fAAV transduction is independent of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in vitro and in vivo while disproportionately reliant on the DNA strand annealing protein Rad51C. Importantly, fAAV's unique dependence on DNA repair proteins, compared with intact AAV, strongly suggests that the majority of oversized AAV transduction is mediated by fragmented genonnes. Although fAAV transduction is less efficient than intact AAV, it is enhanced fourfold in muscle and sevenfold in the retina compared with split AAV transduction. Furthermore, fAAV carrying codon-optimized therapeutic dysferlin cDNA in a 7.5 kb expression cassette restored dysferlin levels in a dystrophic model."
According to the news editors, the research concluded: "Collectively, oversized AAV genome transduction requires unique DNA repair pathways and offers an alternative, more efficient strategy for large-gene therapy."
For more information on this research see: Oversized AAV Transductifon Is Mediated via a DNA-PKcs-independent, Rad51C-dependent Repair Pathway. Molecular Therapy, 2013;21(12):2205-2216. Molecular Therapy can be contacted at: Nature Publishing Group, 75 Varick St, 9TH Flr, New York, NY 10013-1917, USA. (Elsevier - www.elsevier.com; Molecular Therapy - www.elsevier.com/wps/product/cws_home/622922)
Our news journalists report that additional information may be obtained by contacting M.L. Hirsch, University of North Carolina, Dept. of Pharmacol, Chapel Hill, NC 27599, United States. Additional authors for this research include C.W. Li, I. Bellon, C.Y. Yin, S. Chavala, M. Pryadkina, I. Richard and R.J. Samulski (see also technology.html">Biotechnology).
Keywords for this news article include: Biotechnology, Viral DNA, Chapel Hill, DNA Research, Gene Therapy, United States, North Carolina, Bioengineering, North and Central America
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