{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:02:28Z","timestamp":1788850948327,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["EDUC4\u201012751"],"award-info":[{"award-number":["EDUC4\u201012751"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL164588"],"award-info":[{"award-number":["R01 HL164588"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL142579"],"award-info":[{"award-number":["R01HL142579"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32 HL116273"],"award-info":[{"award-number":["T32 HL116273"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    All approved RNA therapeutics require parenteral delivery. Here, we demonstrate an orally bioavailable formulation wherein synthetic noncoding (nc) RNA, packaged into lipid nanoparticles, is loaded into casein\u2010chitosan (C2) micelles. We used the C2 formulation to deliver TY1, a 24\u2010nucleotide synthetic ncRNA, which targets DNA damage and attenuates inflammation in macrophages. C2\u2010formulated TY1 (TY1\n                    <jats:sup>C2<\/jats:sup>\n                    ) efficiently packages and protects TY1 against degradative enzymes. In healthy mice, oral TY1\n                    <jats:sup>C2<\/jats:sup>\n                    was well\u2010tolerated and nontoxic. Oral TY1\n                    <jats:sup>C2<\/jats:sup>\n                    exhibited disease\u2010modifying bioactivity in two models of tissue injury: (1) rat myocardial infarction, where a single oral dose of TY1\n                    <jats:sup>C2<\/jats:sup>\n                    was cardioprotective, on par with intravenously\u2010delivered TY1; and (2) mouse acute lung injury, where a single dose of TY1\n                    <jats:sup>C2<\/jats:sup>\n                    attenuated pulmonary inflammation. Mechanistic dissection revealed that TY1\n                    <jats:sup>C2<\/jats:sup>\n                    is taken up by intestinal macrophages, namely those of the lamina propria and Peyer's patches. Afterwards, TY1 could be detected in circulating monocytes for up to 72 h post\u2010ingestion. Unlike TY1, which acts on macrophages, an antisense oligonucleotide against Factor VII, which acts on hepatocytes, is not effective when administered in the C2 formulation. Thus, not all ncRNA drugs are bioactive when delivered by mouth. Oral delivery of macrophage\u2010active RNA opens up a wide range of potential new therapeutic opportunities.\n                  <\/jats:p>","DOI":"10.1002\/jex2.70081","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:26:31Z","timestamp":1755224791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral Bioavailability of a Noncoding RNA Drug, TY1, That Acts on Macrophages"],"prefix":"10.1002","volume":"4","author":[{"given":"Shukuro","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xaviar M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ciullo","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Tsi","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Anderson","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Komuro","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwa","family":"Soussi","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Morris","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Kitka","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De\u2010Zhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Marb\u00e1n","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-7432","authenticated-orcid":false,"given":"Ahmed G. E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12045"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07774"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022\u20100302(01)74485\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2013.2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12178"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.628137"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.02.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.06.037"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10111906"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","unstructured":"Ibrahim A. 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