{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:59:58Z","timestamp":1792429198153,"version":"4.5.0"},"reference-count":91,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"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":["GEN Biotechnology"],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:p>\n                    Prime editing (PE) has gained significant attention as a next-generation gene editing technology, owing to its unique advantages. However, realizing its potential\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    requires effective delivery strategies. While adeno-associated virus (AAV) has been employed for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    delivery of prime editors in research settings, it presents inherent limitations related to vector size, ongoing expression, and inability to re-dose patients. Conversely, lipid nanoparticles (LNPs) do not face these limitations and are emerging as a leading nonviral approach for the delivery of gene editors. In this study, we demonstrate successful co-delivery of chemically modified pegRNA and prime editor mRNA using LNPs for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    PE. We investigate the impact of pegRNA chemical modifications on editing efficiency and explore different re-dosing regimens. In a daily-repeat dose regimen, we saw striking liver toxicity and no increase in editing; by contrast, weekly repeat dosing was well tolerated and enabled 1.8-fold increase in editing efficacy. Furthermore, in the NOD\n                    <jats:italic toggle=\"yes\">scid<\/jats:italic>\n                    gamma immunodeficient mouse model, the efficacy of LNP-delivered PE was enhanced by 2.8-fold. In addition, the nature of the ionizable lipids and phospholipids strongly influenced PE efficiency\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Overall, these findings will greatly contribute to the future development of LNPs as a robust platform for delivering prime editors\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , fostering progress in PE research and therapeutic applications.\n                  <\/jats:p>","DOI":"10.1089\/genbio.2023.0045","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:09:33Z","timestamp":1702908573000},"page":"490-502","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["<i>In Vivo<\/i>\n                    Prime Editing by Lipid Nanoparticle Co-Delivery of Chemically Modified pegRNA and Prime Editor mRNA"],"prefix":"10.1177","volume":"2","author":[{"given":"Zexiang","family":"Chen","sequence":"first","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA; 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