Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle
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Eghtesad-2012-Effect of rapamycin.pdf
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Author(s)
Eghtesad, Saman
Jhunjhunwala, Siddharth
Little, Steven R.
Clemens, Paula R.
Date Issued
May 2012
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
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).
Version
Final published version
Abstract
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/srep00399
