The role of receptors in the maturation-dependent adenoviral transduction of myofibers

Gene Therapy
Baohong CaoJohnny Huard

Abstract

One of the major hurdles facing the application of adenoviral gene transfer to skeletal muscle is the maturation-dependent transduction of muscle myofibers. It was recently proposed that the viral receptors (Coxsackie and adenovirus receptor (CAR) and the integrins alphavbeta3/beta5) play a major role in the poor adenoviral transduction of mature myofibers. Here we report the findings of morphological studies designed to determine experimentally the role of receptors in the adenoviral transduction of mature myofibers. First, we observed that the expression of both attachment and internalization receptors did not change significantly during muscle development. Second, when an extended tropism adenoviral vector (AdPK) that attaches to heparan sulfate proteoglycan (HSP) is used, a significant reduction of adenoviral transduction still occurs in mature myofibers despite HSP's high expression in mature skeletal muscle fibers. Third, when the adeno-associated virus (AAV) is used, which also utilizes HSP as a viral receptor, muscle fibers at different maturities can be highly transduced. Fourth, the pre-irradiation of the skeletal muscle of newborn mice to inactivate myoblasts dramatically decreased the transduction level of Ad and Ad...Continue Reading

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Citations

Aug 15, 2012·Human Gene Therapy·Kilian GuseBrendan Lee
Mar 5, 2003·Circulation·Catherine CommunalRoger J Hajjar
Jul 21, 2010·Journal of Visualized Experiments : JoVE·Yong LiJohnny Huard
Feb 20, 2008·Biology of the Cell·Andrea C M SinananMark P Lewis
Sep 18, 2015·BioMed Research International·Natalia SmolinaThomas Sejersen
Oct 16, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Rénald GilbertGeorge Karpati
Nov 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jin Zhong LiGregory A Helm
Jul 12, 2002·Microscopy Research and Technique·Baohong CaoJohnny Huard
Jan 25, 2006·The Journal of General Virology·Sandra VerhaaghMenzo Havenga

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