{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:19:36Z","timestamp":1787728776753,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    GNE myopathy is an autosomal recessive disease, associated with skeletal muscle deterioration, which afflicts young adults. GNE plays a pivotal role in sialic acid production. Sialic acid acts as a buffer against reactive oxygen species generated during muscle contraction. Increased oxidative stress may relate to muscle atrophy involving patients with GNE myopathy. GNE\n                    <jats:sup>M743T<\/jats:sup>\n                    is the most common mutation leading to GNE myopathy. In our previous work, we demonstrated that a bifunctional plasmid that expresses wild type (wt) GNE and knocks down the GNE\n                    <jats:sup>M743T<\/jats:sup>\n                    mutant improves sialic acid production in\u00a0vitro. Now, we expand evidence of in\u00a0vivo activity of the bifunctional plasmid using a DOTAP\u2010Cholesterol delivery vehicle and reduced toxic plasmid components using dbDNA conversion. We demonstrate that IV delivery of dbDNA lipoplex (LPX) in murine and rat models shows safety, increased DNA delivery, and improved RNA expression per LPX in skeletal muscle over non db plasmid at equal dose. Sialic acid protein expression was also shown increased in mouse muscle following IV treatment with dbDNA plasmid (pDNA) GNE\n                    <jats:sup>wt<\/jats:sup>\n                    \/bi\u2010shRNA\u2010GNE\n                    <jats:sup>M743T<\/jats:sup>\n                    LPX. These results support further preclinical investigation to justify product IND development towards Phase 1 trial involving patients with GNE myopathy.\n                  <\/jats:p>","DOI":"10.1002\/jgm.70098","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:16:47Z","timestamp":1779779807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vivo Assessment of dbDNA GNE\n                    <sup>wt<\/sup>\n                    \/bi\u2010shRNA\u2010GNE\n                    <sup>M743T<\/sup>\n                    Lipoplex for GNE Myopathy: Improved Potency and Safety"],"prefix":"10.1002","volume":"28","author":[{"given":"Christopher M.","family":"Jay","sequence":"first","affiliation":[{"name":"Gradalis Inc  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Kerneis","sequence":"additional","affiliation":[{"name":"Gradalis Inc  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