{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:45:22Z","timestamp":1788317122788,"version":"build-2803163510"},"reference-count":28,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-183929"],"award-info":[{"award-number":["PJT-183929"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Methods & Clinical Development"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.omtm.2025.101583","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T15:38:16Z","timestamp":1756741096000},"page":"101583","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vivo delivery of a fluorogenic antisense oligonucleotide into human leukocytes in a humanized mouse model system"],"prefix":"10.1016","volume":"33","author":[{"given":"Nathan B.","family":"Seidel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav S.","family":"Rout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly Z.","family":"Packard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-4546","authenticated-orcid":false,"given":"Kerry J.","family":"Lavender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101583_bib1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.addr.2016.01.022","article-title":"The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery","volume":"99","author":"Cheng","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.omtm.2025.101583_bib2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1089\/nat.2022.0004","article-title":"Delivery of RNA Therapeutics: The Great Endosomal Escape","volume":"32","author":"Dowdy","year":"2022","journal-title":"Nucleic Acid Ther."},{"key":"10.1016\/j.omtm.2025.101583_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/cells12182253","article-title":"Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking","volume":"12","author":"Mangla","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.omtm.2025.101583_bib4","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1093\/nar\/gkad067","article-title":"Chemistry, structure and function of approved oligonucleotide therapeutics","volume":"51","author":"Egli","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2025.101583_bib5","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202013243","article-title":"Delivery of oligonucleotide-based therapeutics: challenges and opportunities","volume":"13","author":"Hammond","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.omtm.2025.101583_bib6","doi-asserted-by":"crossref","first-page":"7132","DOI":"10.7150\/thno.77830","article-title":"Specificity of oligonucleotide gene therapy (OGT) agents","volume":"12","author":"Nedorezova","year":"2022","journal-title":"Theranostics"},{"key":"10.1016\/j.omtm.2025.101583_bib7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41573-020-0075-7","article-title":"Advances in oligonucleotide drug delivery","volume":"19","author":"Roberts","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.omtm.2025.101583_bib8","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1038\/s41467-021-26902-8","article-title":"DNA\/RNA heteroduplex oligonucleotide technology for regulating lymphocytes in vivo","volume":"12","author":"Ohyagi","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omtm.2025.101583_bib9","first-page":"147","article-title":"Targeting the HIV RNA genome: high-hanging fruit only needs a longer ladder","volume":"389","author":"Le Grice","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"10.1016\/j.omtm.2025.101583_bib10","doi-asserted-by":"crossref","first-page":"11640","DOI":"10.1073\/pnas.93.21.11640","article-title":"Profluorescent protease substrates: intramolecular dimers described by the exciton model","volume":"93","author":"Packard","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101583_bib11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0076-6879(97)78004-2","article-title":"Design of profluorescent protease substrates guided by exciton theory","volume":"278","author":"Packard","year":"1997","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.omtm.2025.101583_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0076-6879(08)03401-0","article-title":"A method in enzymology for measuring hydrolytic activities in live cell environments","volume":"450","author":"Packard","year":"2008","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.omtm.2025.101583_bib13","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1002\/cyto.a.24174","article-title":"An Oligonucleotide Delivery Platform to Enable Assessment of Intracellular Transcripts in Live Cells by Flow Cytometry","volume":"97","author":"Packard","year":"2020","journal-title":"Cytometry. A."},{"key":"10.1016\/j.omtm.2025.101583_bib14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.virusres.2012.07.004","article-title":"HIV RNA dimerisation interference by antisense oligonucleotides targeted to the 5' UTR structural elements","volume":"169","author":"Reyes-Darias","year":"2012","journal-title":"Virus Res."},{"key":"10.1016\/j.omtm.2025.101583_bib15","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/jp972845b","article-title":"Intramolecular Resonance Dipole\u2212Dipole Interactions in a Profluorescent Protease Substrate","volume":"102","author":"Packard","year":"1998","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.omtm.2025.101583_bib16","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1021\/acs.jpcb.4c07517","article-title":"The Influence of Length and Sequence of Complementary Oligonucleotides on the Spectral and Time-Resolved Fluorescence Properties of an H-Type Excitonic Dimer-Bearing Antisense Oligonucleotide","volume":"129","author":"Packard","year":"2025","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.omtm.2025.101583_bib17","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1084\/jem.191.11.1819","article-title":"Assessment of caspase activities in intact apoptotic thymocytes using cell-permeable fluorogenic caspase substrates","volume":"191","author":"Komoriya","year":"2000","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.omtm.2025.101583_bib18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jim.2014.04.008","article-title":"Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL\/6 Rag2(-\/-)gammac(-\/-)CD47(-\/-) background","volume":"407","author":"Lavender","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.omtm.2025.101583_bib19","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1182\/blood-2013-06-506949","article-title":"BLT-humanized C57BL\/6 Rag2-\/-gammac-\/-CD47-\/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection","volume":"122","author":"Lavender","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2025.101583_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9062004","article-title":"Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development","volume":"9","author":"Dhuri","year":"2020","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.omtm.2025.101583_bib21","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1001\/jama.282.17.1627","article-title":"Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy","volume":"282","author":"Dornadula","year":"1999","journal-title":"JAMA"},{"key":"10.1016\/j.omtm.2025.101583_bib22","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1073\/pnas.1917876117","article-title":"Defective HIV-1 proviruses produce viral proteins","volume":"117","author":"Imamichi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101583_bib23","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.1073\/pnas.1609057113","article-title":"Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy","volume":"113","author":"Imamichi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101583_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2021.101471","article-title":"Residual immune dysfunction under antiretroviral therapy","volume":"51","author":"Cai","year":"2021","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.omtm.2025.101583_bib25","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s12035-024-04285-3","article-title":"From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer's Disease","volume":"62","author":"Ortega","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.omtm.2025.101583_bib26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"10.1016\/j.omtm.2025.101583_bib27","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.cell.2015.11.013","article-title":"Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors","volume":"163","author":"Paul","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2025.101583_bib28","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1096\/fj.201700753R","article-title":"beta-Actin-dependent global chromatin organization and gene expression programs control cellular identity","volume":"32","author":"Xie","year":"2018","journal-title":"FASEB J."}],"container-title":["Molecular Therapy Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125001780?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125001780?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:31:29Z","timestamp":1776198689000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050125001780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S2329050125001780"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101583","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vivo delivery of a fluorogenic antisense oligonucleotide into human leukocytes in a humanized mouse model system","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101583","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"101583"}}