Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle
Author(s)Eghtesad, Saman; Jhunjhunwala, Siddharth; Little, Steven R.; Clemens, Paula R.
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Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Therapeutic gene replacement of a dystrophin cDNA into dystrophic muscle can provide functional dystrophin protein to the tissue. However, vector-mediated gene transfer is limited by anti-vector and anti-transgene host immunity that causes rejection of the therapeutic protein. We hypothesized that rapamycin (RAPA) would diminish immunity due to vector-delivered recombinant dystrophin in the adult mdx mouse model for DMD. To test this hypothesis, we injected limb muscle of mdx mice with RAPA-containing, poly-lactic-co-glycolic acid (PLGA) microparticles prior to dystrophin gene transfer and analyzed treated tissue after 6 weeks. RAPA decreased host immunity against vector-mediated dystrophin protein, as demonstrated by decreased cellular infiltrates and decreased anti-dystrophin antibody production. The interpretation of the effect of RAPA on recombinant dystrophin expression was complex because of an effect of PLGA microparticles.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT
Nature Publishing Group
Eghtesad, Saman, Siddharth Jhunjhunwala, Steven R. Little, and Paula R. Clemens. “Effect of Rapamycin on Immunity Induced by Vector-Mediated Dystrophin Expression in Mdx Skeletal Muscle.” Sci. Rep. 2 (May 8, 2012).
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