{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:45:34Z","timestamp":1791081934333,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Engineering RNA stability has become a cornerstone of modern therapeutics, almost entirely in one direction: mRNA vaccines established\n                    <jats:italic>stabilisation<\/jats:italic>\n                    of exogenous transcripts as a powerful design axis. The symmetric operation\u2014\n                    <jats:italic>exploitation<\/jats:italic>\n                    of instability in endogenous targets\u2014has been comparatively underexplored. We argue that target RNA half\u2010life is an underused but quantitatively consequential design parameter for antisense oligonucleotide (ASO) therapeutics, and that short\u2010lived long noncoding RNAs (lncRNAs) are a particularly attractive target class. Under sustained ASO dosing, the time to a new steady state is set by the sum of the target's own decay rate and the ASO\u2010induced decay rate, so\u2014for a given depth of knockdown\u2014endogenous half\u2010life becomes a major determinant of pharmacodynamic onset alongside ASO potency and delivery, most directly for RNase H\u2010dependent gapmers; we treat the resulting first\u2010order relationships as a qualitative design heuristic rather than a quantitative pharmacokinetic\/pharmacodynamic model. Two back\u2010to\u2010back 2012 surveys\u2014BRIC\u2010seq in human HeLa and actinomycin\u2010D microarray in mouse Neuro\u20102a\u2014yielded similar median lncRNA half\u2010lives of 3.4 and 3.5\u2009h, with a short\u2010lived fraction we term short\u2010lived noncoding transcripts (SLiTs;\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    \u2009&lt;\u20094\u2009h). SLiTs include several disease\u2010relevant regulators (GAS5, NEAT1, CDKN2B\u2010AS1\/ANRIL, HOTAIR, TUG1); their rapid turnover supports fast onset, reversibility and tight titratability. We (i) develop a kinetic framework for how target half\u2010life shapes ASO pharmacodynamic onset, (ii) survey the cross\u2010species half\u2010life landscape, (iii) propose a\n                    <jats:italic>decay\u2010pathway\u2010aware ASO design<\/jats:italic>\n                    framework aligning modality choice with endogenous decay machinery, (iv) re\u2010read representative clinical ASO cases (nusinersen, tofersen, tominersen, MALAT1 ASOs) through the half\u2010life lens, and (v) outline a half\u2010life\u2010aware preclinical roadmap. Treating half\u2010life symmetrically\u2014engineered up in vaccine RNAs, exploited downward in endogenous targets\u2014highlights a largely unoccupied design space for next\u2010generation oligonucleotide therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/iub.70122","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:12:26Z","timestamp":1783739546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Half\u2010Life as a Therapeutic Design Axis: Targeting Short\u2010Lived\n                    <scp>lncRNAs<\/scp>\n                    With Antisense Oligonucleotides"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-4136","authenticated-orcid":false,"given":"Hidenori","family":"Tani","sequence":"first","affiliation":[{"name":"Department of Health Pharmacy Yokohama University of Pharmacy  Yokohama 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