{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:50:12Z","timestamp":1791640212987,"version":"4.3.4"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015834","name":"Ono Pharma Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015834","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ellison Foundation of Lynn"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD020012"],"award-info":[{"award-number":["S10 OD020012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nucleic Acid Chemistry Center","award":["S10 OD028576"],"award-info":[{"award-number":["S10 OD028576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has been challenging to determine their effectiveness in each cell type due to the lack of appropriate analytical methods. We employed three distinct approaches to study silencing efficacy within different cell types. First, we used lineage markers to identify cell types in flow cytometry, and simultaneously measured ASO-induced silencing of cell-surface proteins CD47 or CD98. Second, we applied single-cell RNA sequencing (scRNA-seq) to measure silencing efficacy in distinct cell types; to the best of our knowledge, this is the first time scRNA-seq has been applied to measure the efficacy of oligonucleotide therapeutics. In both approaches, fibroblasts were the most susceptible to locally delivered ASOs, with significant silencing also in endothelial cells. Third, we confirmed that the robust silencing in fibroblasts is broadly applicable by silencing two targets expressed mainly in fibroblasts, Mfap4 and Adam33. Across independent approaches, we demonstrate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibroblasts. ASO-induced gene silencing in fibroblasts was durable, lasting 4\u20138 weeks after a single dose. Thus, lung fibroblasts are well aligned with ASOs as therapeutics.<\/jats:p>","DOI":"10.1093\/nar\/gkac630","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T10:39:28Z","timestamp":1659523168000},"page":"8418-8430","source":"Crossref","is-referenced-by-count":33,"title":["Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts"],"prefix":"10.1093","volume":"50","author":[{"given":"Minwook","family":"Shin","sequence":"first","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Chan Medical School , Worcester, MA\u00a001605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Io Long","family":"Chan","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Chan Medical School , Worcester, MA\u00a001605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Cao","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School , Worcester, MA\u00a001605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha M","family":"Gruntman","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Chan Medical School , Worcester, MA\u00a001605, USA"},{"name":"Department of Pediatrics, University of Massachusetts Chan Medical School , Worcester, MA 01605, USA"},{"name":"Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University , N. 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Ther."},{"key":"2022082600045841400_B56","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.addr.2015.01.008","article-title":"Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides","volume":"87","author":"Geary","year":"2015","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"2022082600045841400_B57","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1089\/nat.2017.0716","article-title":"Current challenges in delivery and cytosolic translocation of therapeutic RNAs","volume":"28","author":"Johannes","year":"2018","journal-title":"Nucleic Acid Ther."},{"key":"2022082600045841400_B58","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ymthe.2006.05.017","article-title":"Efficient and persistent splice switching by systemically delivered LNA oligonucleotides in mice","volume":"14","author":"Roberts","year":"2006","journal-title":"Mol. 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Biol."},{"key":"2022082600045841400_B63","doi-asserted-by":"crossref","first-page":"e36865","DOI":"10.7554\/eLife.36865","article-title":"Pdgfra marks a cellular lineage with distinct contributions to myofibroblasts in lung maturation and injury response","volume":"7","author":"Li","year":"2018","journal-title":"Elife"},{"key":"2022082600045841400_B64","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.omtn.2019.02.013","article-title":"Intratracheal administration of siRNA triggers mRNA silencing in the lung to modulate t cell immune response and lung inflammation","volume":"16","author":"Ng","year":"2019","journal-title":"Mol. 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Commun."},{"key":"2022082600045841400_B72","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1165\/rcmb.2003-0028OC","article-title":"Human ADAM33 messenger RNA expression profile and post-transcriptional regulation","volume":"29","author":"Umland","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2022082600045841400_B73","doi-asserted-by":"crossref","first-page":"e87632","DOI":"10.1172\/jci.insight.87632","article-title":"Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life","volume":"1","author":"Davies","year":"2016","journal-title":"JCI Insight"},{"key":"2022082600045841400_B74","doi-asserted-by":"crossref","first-page":"eabl4896","DOI":"10.1126\/science.abl4896","article-title":"The tabula sapiens: a multiple-organ, single-cell transcriptomic atlas of humans","volume":"376","year":"2022","journal-title":"Science"},{"key":"2022082600045841400_B75","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-018-0590-4","article-title":"Single-cell transcriptomics of 20 mouse organs creates a tabula muris","volume":"562","author":"The Tabula Muris Consortium","year":"2018","journal-title":"Nature"},{"key":"2022082600045841400_B76","doi-asserted-by":"crossref","first-page":"eaah4573","DOI":"10.1126\/science.aah4573","article-title":"Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors","volume":"356","author":"Villani","year":"2017","journal-title":"Science"},{"key":"2022082600045841400_B77","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1021\/mp050012x","article-title":"Biodistribution and hepatic uptake of triplex-forming oligonucleotides against type alpha1(I) collagen gene promoter in normal and fibrotic rats","volume":"2","author":"Cheng","year":"2005","journal-title":"Mol. Pharm."},{"key":"2022082600045841400_B78","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1093\/nar\/gku531","article-title":"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice","volume":"42","author":"Prakash","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2022082600045841400_B79","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/nar\/gkaa1235","article-title":"The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration","volume":"49","author":"Jafar-Nejad","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022082600045841400_B80","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.tips.2021.04.010","article-title":"Overcoming the challenges of tissue delivery for oligonucleotide therapeutics","volume":"42","author":"Gokirmak","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"2022082600045841400_B81","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.3390\/ijms21062064","article-title":"Sphingosine kinase 1\/S1P signaling contributes to pulmonary fibrosis by activating Hippo\/YAP pathway and mitochondrial reactive oxygen species in lung fibroblasts","volume":"21","author":"Huang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2022082600045841400_B82","doi-asserted-by":"crossref","first-page":"11802","DOI":"10.1096\/fj.202001045RR","article-title":"Fibroblast-specific IL11 signaling drives chronic inflammation in murine fibrotic lung disease","volume":"34","author":"Ng","year":"2020","journal-title":"FASEB J."},{"key":"2022082600045841400_B83","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1164\/rccm.201807-1237OC","article-title":"The long noncoding RNA DNM3OS is a reservoir of fibromirs with major functions in lung fibroblast response to TGF-beta and pulmonary fibrosis","volume":"200","author":"Savary","year":"2019","journal-title":"Am. J. Respir. Crit. 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