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Injection risks and logistics lower patient compliance; however, even patients receiving optimal treatment can deteriorate. Gene silencing has shown great potential as a therapeutic alternative but is often limited by instability of the genetic payload, reducing efficacy. In the current work, a cationic block co\u2010polymer was developed and investigated as a delivery system for an antisense oligonucleotide (ASO) to the posterior segment of the eye. This work details the synthesis, characterization, in\u00a0vitro, and ex\u00a0vivo testing of the polymer and the subsequent polyplexes formed between the polymer and ASO. pH\u2010dependent polyplexes were formed which fully complexed the ASO at 1:1 and 10:1 ratios of polymer amine groups to ASO phosphate groups (N\/P ratio). Neither formulation displayed a significant reduction in the viability of human retinal pigment epithelial (ARPE\u201019) cells. The polyplexes were under 150\u2009nm in diameter, with a slightly negative zeta potential. In comparison to the naked ASO, the 10:1 polyplexes achieved superior transfection into ARPE\u201019 cells. After 24\u2009h, the ASO delivered by the 10:1 polyplexes displayed significant knockdown of the target protein. Polyplexes were well distributed throughout the vitreous humor, retina, and choroid within 4\u2009h of intravitreal administration in an ex\u00a0vivo porcine eye. These materials show potential for gene delivery in the treatment of various posterior segment conditions including nAMD.<\/jats:p>","DOI":"10.1002\/jbm.a.70078","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:46:03Z","timestamp":1777466763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cationic Block Co\u2010Polymer for Gene Delivery in the Posterior Segment of the Eye"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1868-5974","authenticated-orcid":false,"given":"Amber","family":"Monteiro","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4519-6727","authenticated-orcid":false,"given":"Odunayo O.","family":"Mugisho","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"de Souza","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosra","family":"Agban","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avik","family":"Shome","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-5994","authenticated-orcid":false,"given":"Ilva D.","family":"Rupenthal","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa\u2010New Zealand National Eye Centre, Faculty of Medical and Health Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Sheardown","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010021\u201000265\u20102"},{"issue":"1","key":"e_1_2_8_3_1","first-page":"9","article-title":"Wet Age Related Macular Degeneration Management and Follow\u2010Up","volume":"60","author":"Alexandru M. 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