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Therapeutic attempts to restore a functional copy of dystrophin to striated muscle are under active development, and many utilize adeno-associated viral (AAV) vectors. However, the limited cargo capacity of AAVs precludes delivery of full-length dystrophin, a 427 kDa protein, to target tissues. Recently, we developed a method to express large dystrophin constructs using the protein\n                    <jats:italic>trans<\/jats:italic>\n                    -splicing mechanism mediated by split inteins and myotropic AAV vectors. The efficacy of this approach to restore muscle function in\n                    <jats:italic>mdx<\/jats:italic>\n                    <jats:sup>4cv<\/jats:sup>\n                    mice was previously assessed using histology, dystrophin immunolabeling, and Western blotting. Here, we expand our molecular characterization of dystrophin constructs with variable lengths using a mass spectrometry\u2013based proteomics approach, providing insight into unique protein expression profiles in skeletal muscles of wild-type, dystrophic\n                    <jats:italic>mdx<\/jats:italic>\n                    <jats:sup>4cv<\/jats:sup>\n                    , and AAV-treated\n                    <jats:italic>mdx<\/jats:italic>\n                    <jats:sup>4cv<\/jats:sup>\n                    mice. Our data reveal several affected cellular processes in\n                    <jats:italic>mdx<\/jats:italic>\n                    <jats:sup>4cv<\/jats:sup>\n                    skeletal muscles with changes in the expression profiles of key proteins to muscle homeostasis, whereas successful expression of dystrophin constructs results in an intermediate to complete restoration. This study highlights several biomarkers that could be used in future preclinical or clinical studies to evaluate the effectiveness of therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.197759","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T17:00:17Z","timestamp":1764262817000},"source":"Crossref","is-referenced-by-count":1,"title":["Proteomics-based evaluation of AAV dystrophin gene therapy outcomes in mdx skeletal muscle"],"prefix":"10.1172","volume":"11","author":[{"given":"Erynn E.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore R.","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Neurology,"},{"name":"Senator Paul D. 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