{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:56:41Z","timestamp":1792598201175,"version":"4.5.0"},"reference-count":100,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-050578"],"award-info":[{"award-number":["INV-050578"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH)","award":["AI161803"],"award-info":[{"award-number":["AI161803"]}]},{"name":"National Institutes of Health (NIH)","award":["AI172410"],"award-info":[{"award-number":["AI172410"]}]},{"name":"National Institutes of Health (NIH)","award":["CA031845"],"award-info":[{"award-number":["CA031845"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circular RNA is a therapeutically promising RNA modality with superior stability and extended protein expression relative to linear RNA. While delivery systems for linear RNA have received much attention, less effort has been directed toward the delivery of circular RNA, whose closed topology and physicochemical properties differ from those of linear RNAs. Here, we disclose a class of ionizable lipids that enable efficient in vitro and in vivo delivery of circular RNA. These ionizable lipids are step-economically accessible, allowing facile assessment of their structure\u2013delivery relationships. Our studies reveal key elements that enhance circular RNA delivery in vitro and in vivo, including aminoethoxy head units, doubly branched tails and linkers tuned for hydrogen bonding and biodegradability. The lead ionizable lipid for circular RNA delivery, iL-19, incorporating these features, achieves \u223c28-fold higher protein expression in C2C12 myocytes than Moderna\u2019s SM-102 formulation and 2.5-fold higher expression upon intramuscular administration in BALB\/c mice. iL-19 also surpasses benchmark ionizable lipids ALC-0315 (7.8-fold) and DLin-MC3-DMA (33.4-fold) for intramuscular circular RNA delivery in vivo under otherwise identical conditions. This study establishes design principles and a step-economical synthesis for accessing ionizable lipids that enable highly efficient in vitro and in vivo circular RNA delivery.<\/jats:p>","DOI":"10.1021\/jacs.6c14175","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:01:49Z","timestamp":1791644509000},"page":"44730-44738","source":"Crossref","is-referenced-by-count":0,"title":["Circular RNA Delivery\nIn Vitro and In Vivo Using Doubly\nBranched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles"],"prefix":"10.1021","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6624-041X","authenticated-orcid":true,"given":"Adam","family":"Cook","sequence":"first","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-2320","authenticated-orcid":true,"given":"Pavan K.","family":"Yadav","sequence":"additional","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekram W.","family":"Helmy","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Vlasova","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard Y.","family":"Chang","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6319-2829","authenticated-orcid":true,"given":"Paul A.","family":"Wender","sequence":"additional","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Stanford University School of Medicine , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"2026102111084634300_cit1","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","article-title":"The clinical\nprogress of mRNA vaccines and immunotherapies","volume":"40","author":"Barbier","year":"2022","journal-title":"Nat. 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Nanotechnol."},{"key":"2026102111084634300_cit2c","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e24606","article-title":"Lipid Nanoparticles: The Game-Changer in CRISPR-Cas9\nGenome Editing","volume":"10","author":"Mohammadian Farsani","year":"2024","journal-title":"Heliyon"},{"key":"2026102111084634300_cit3a","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41586-020-2537-9","article-title":"An RNA vaccine drives\nimmunity in checkpoint-inhibitor-treated\nmelanoma","volume":"585","author":"Sahin","year":"2020","journal-title":"Nature"},{"key":"2026102111084634300_cit3b","doi-asserted-by":"publisher","first-page":"24302","DOI":"10.1021\/jacs.3c09143","article-title":"Modular design of biodegradable ionizable lipids for improved mRNA\ndelivery and precise cancer metastasis delineation in vivo","volume":"145","author":"Chen","year":"2023","journal-title":"J. Am. Chem. 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