{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:20:36Z","timestamp":1787498436491,"version":"build-2736575974"},"reference-count":38,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"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":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:p>\n                    Recent advances in the therapeutic potential of RNA-related treatments, specifically for antisense oligonucleotide (ASO)-based drugs, have led to increased numbers of ASO regulatory approvals. In this study, we focus on SPL84, an inhaled ASO-based drug, developed for the treatment of the pulmonary disease cystic fibrosis (CF). Pulmonary drug delivery is challenging, due to a variety of biological, physical, chemical, and structural barriers, especially when targeting the cell nucleus. The distribution of SPL84 throughout the lungs, penetration into the epithelial cells and nucleus, and structural stability are critical parameters that will impact drug efficacy in a clinical setting. In this study, we demonstrate broad distribution, as well as cell and nucleus penetration of SPL84 in mouse and monkey lungs.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    studies confirmed the stability of our inhaled drug in CF patient-derived mucus and in lung lysosomal extracts. The mobility of SPL84 through hyperconcentrated mucus was also demonstrated. Our results, supported by a promising preclinical pharmacological effect of full restoration of cystic fibrosis transmembrane conductance regulator channel activity, emphasize the high potential of SPL84 as an effective drug for the treatment of CF patients. In addition, successfully tackling the lung distribution of SPL84 offers immense opportunities for further development of SpliSense's inhaled ASO-based drugs for unmet needs in pulmonary diseases.\n                  <\/jats:p>","DOI":"10.1089\/nat.2023.0015","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T14:31:37Z","timestamp":1693319497000},"page":"306-318","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849\u2009+\u200910\u2009kb C- &gt; T Cystic Fibrosis Patients"],"prefix":"10.1177","volume":"33","author":[{"given":"Efrat","family":"Ozeri-Galai","sequence":"first","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lital","family":"Friedman","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-5309","authenticated-orcid":false,"given":"Ofra","family":"Barchad-Avitzur","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Markovetz","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, UNC Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Boone","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, UNC Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn R.","family":"Rouillard","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, UNC Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chava D.","family":"Stampfer","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifat S.","family":"Oren","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Hill","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, UNC Chapel Hill, Chapel Hill, North Carolina, USA."},{"name":"Joint Department of Biomedical Engineering, UNC Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batsheva","family":"Kerem","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."},{"name":"Department of Genetics, The Hebrew University, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Hart","sequence":"additional","affiliation":[{"name":"SpliSense, Biohouse Labs, Haddasah Ein Kerem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00184B"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105654"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3625"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2018.4"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-020-0156-6"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013243"},{"key":"e_1_3_5_8_2","author":"Orenti A","year":"2022","unstructured":"Orenti A, , Zolin A, , Jung A, , van Rens J, , Fox A, , Krasnyk M, , Daneau G, , Hatziagorou E, , Mei-Zahav M, et al. 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