title: Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle.
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.
authors.forename: Saman
authors.initials: S
authors.lastname: Eghtesad
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
authors.forename: Paula R
authors.initials: PR
authors.lastname: Clemens