dc.contributor.author | Eghtesad, Saman | |
dc.contributor.author | Jhunjhunwala, Siddharth | |
dc.contributor.author | Little, Steven R. | |
dc.contributor.author | Clemens, Paula R. | |
dc.date.accessioned | 2014-07-09T13:54:42Z | |
dc.date.available | 2014-07-09T13:54:42Z | |
dc.date.issued | 2012-05 | |
dc.date.submitted | 2011-12 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/88225 | |
dc.description.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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (F31-NS056780-01A2) | en_US |
dc.description.sponsorship | National Center for Research Resources (U.S.) (KL2 RR024154) | en_US |
dc.description.sponsorship | United States. Army Medical Research and Materiel Command (grant W81XWH-05-1-0334) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/srep00399 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en_US |
dc.source | Nature Publishing Group | en_US |
dc.title | Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle | en_US |
dc.type | Article | en_US |
dc.identifier.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). | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Jhunjhunwala, Siddharth | en_US |
dc.relation.journal | Scientific Reports | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Eghtesad, Saman; Jhunjhunwala, Siddharth; Little, Steven R.; Clemens, Paula R. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8046-2288 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |