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Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids\u2014CRISPR\u2010Cas9 genome\u2010editing system and a therapeutic gene, Retinoschisin 1 (RS1)\u2014enabling clustered regularly interspaced short palindromic repeats (CRISPR)\u2010associated protein 9 (CRISPR\/Cas9) knockin of the RS1 gene with HITI. Through small\u2010scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)\u2010plasmid in one and Donor\u2010RS1 and green fluorescent protein (GFP)\u2010plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR\/Cas9 knockin of RS1\/GFP genes into the mouse Rosa26 safe\u2010harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single\u2010copy 3.0\u2010kb RS1\/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1\/GFP gene is expressed in the retinas, demonstrating CRISPR\/Cas9 knockin of RS1\/GFP gene.<\/jats:p>","DOI":"10.1002\/advs.201903432","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T02:16:07Z","timestamp":1587089767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Dual Supramolecular Nanoparticle Vectors Enable CRISPR\/Cas9\u2010Mediated Knockin of Retinoschisin 1 Gene\u2014A Potential Nonviral Therapeutic Solution for X\u2010Linked Juvenile Retinoschisis"],"prefix":"10.1002","volume":"7","author":[{"given":"Shih\u2010Jie","family":"Chou","sequence":"first","affiliation":[{"name":"Division of Basic Research Department of Medical Research and Department of Ophthalmology Taipei Veterans General 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