By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Research findings on Cardiology are discussed in a new report. According to news reporting originating in Trieste, Italy, by NewsRx journalists, research stated, "Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive."
The news reporters obtained a quote from the research from Molecular Medicine Laboratory, "Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction."
According to the news reporters, the research concluded: "Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction."
For more information on this research see: Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins. Molecular Therapy, 2012;20(11):2087-97. (Elsevier - www.elsevier.com; Molecular Therapy - www.elsevier.com/wps/product/cws_home/622922)
Our news correspondents report that additional information may be obtained by contacting J. Lovric, Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy. Additional authors for this research include M. Mano, L. Zentilin, A. Eulalio, S. Zacchigna and M. Giacca (see also Cardiology).
Keywords for this news article include: Biotechnology, Italy, Europe, Trieste, Peptides, Proteins, Viral DNA, Cardiology, DNA Damage, Proteomics, Amino Acids, DNA Research, Gene Therapy, Bioengineering, Deoxyribonucleic Acid.
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