{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:02:45Z","timestamp":1792638165728,"version":"4.5.0"},"reference-count":41,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      Antisense oligonucleotide (AON)-mediated exon skipping is a potential therapeutic approach to certain inherited retinal diseases, including Usher\u2019s Syndrome Type 2 A. Heteroduplex AONs (HAONs) have been reported to enhance RNA-modulating activity\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      ; this study evaluated whether the HAON strategy improves\n                      <jats:italic toggle=\"yes\">Ush2a<\/jats:italic>\n                      exon skipping activity in the mouse retina.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      AONs of different chemical makeup targeting\n                      <jats:italic toggle=\"yes\">Ush2a<\/jats:italic>\n                      exon 12 were formulated as HAONs with and without lipid conjugation. Activity was evaluated in 2D and 3D cell models and in the mouse eye following intravitreal administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Lipid conjugation was required to increase activity in the mouse retina. However, exon-skipping effects observed for cholesterol (Chol)-conjugated HAONs\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      were not reflected in cell models. A single dose of HAONs bearing a Chol on either strand or the Chol\u2013AON conjugate produced up to a 4.6-fold increase in\n                      <jats:italic toggle=\"yes\">Ush2a<\/jats:italic>\n                      exon 12 skipping in mouse retina over AON alone, with effects lasting at least 28 days without major tolerability findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Chol conjugation\u2014either to a HAON construct or directly to the AON\u2014can substantially enhance the potency of retina-targeted exon-skipping AON therapies\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261469047","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:58:28Z","timestamp":1784530708000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cholesterol Conjugation Strategies to Enhance\n                    <i>In Vivo<\/i>\n                    Antisense Oligonucleotide-Mediated Exon Skipping in the Mouse Retina"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-1115","authenticated-orcid":false,"given":"Peter C.","family":"de Visser","sequence":"first","affiliation":[{"name":"ProQR Therapeutics, Leiden, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian N.","family":"Bangel","sequence":"additional","affiliation":[{"name":"ProQR Therapeutics, Leiden, The 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