دورية أكاديمية
أعرض في EDS

Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection.

التفاصيل البيبلوغرافية
العنوان: Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection.
المؤلفون: Qiao Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America.; Department of Pathology, University of Michigan, Ann Arbor, MI, United States of America.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, United States of America., Wotring JW; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States of America., Zhang CJ; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States of America., Jiang X; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America., Xiao L; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America., Watt A; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Gattis D; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Scandalis E; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Freier S; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Zheng Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America., Pretto CD; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America., Ellison SJ; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America., Swayze EE; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Guo S; Ionis Pharmaceuticals, Carlsbad, CA, United States of America., Sexton JZ; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States of America.; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.; Center for Drug Repurposing, University of Michigan, Ann Arbor, MI, United States of America.; Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, United States of America., Chinnaiyan AM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, United States of America.; Department of Pathology, University of Michigan, Ann Arbor, MI, United States of America.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, United States of America.; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, United States of America.; Department of Urology, University of Michigan, Ann Arbor, MI, United States of America.
المصدر: PloS one [PLoS One] 2023 Feb 03; Vol. 18 (2), pp. e0281281. Date of Electronic Publication: 2023 Feb 03 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: SARS-CoV-2*/genetics , COVID-19*, Humans ; Angiotensin-Converting Enzyme 2/metabolism ; Oligonucleotides, Antisense/pharmacology ; Oligonucleotides, Antisense/therapeutic use ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Virus Internalization
مستخلص: Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)-short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted against the SARS-CoV-2 genome and host entry factors, ACE2 and TMPRSS2, were designed and tested for their ability to inhibit cellular infection by SARS-CoV-2. Using our previously developed SARS-CoV-2 bioassay platform, we screened 180 total ASOs targeting various regions of the SARS-CoV-2 genome and validated several ASOs that potently blocked SARS-CoV-2 infection in vitro. Notably, select ASOs retained activity against both the WA1 and B.1.1.7 (commonly known as alpha) variants. Screening of ACE2 and TMPRSS2 ASOs showed that targeting of ACE2 also potently prevented infection by the WA1 and B.1.1.7 SARS-CoV-2 viruses in the tested cell lines. Combined with the demonstrated success of ASOs in other disease indications, these results support further research into the development of ASOs targeting SARS-CoV-2 and host entry factors as potential COVID-19 therapeutics.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.W., D.G., E.S., S.F., E.E.S., and S.G. are employees of Ionis Pharmaceuticals. The remaining authors have no competing interests. We did not receive any financial support from Ionis Pharmaceuticals; they just provided the antisense oligonucleotides for the study (ASOs).
(Copyright: © 2023 Qiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: R01 DK120623 United States DK NIDDK NIH HHS; United States HHMI Howard Hughes Medical Institute
المشرفين على المادة: EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
0 (Oligonucleotides, Antisense)
EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SCR Organism: SARS-CoV-2 variants
تواريخ الأحداث: Date Created: 20230203 Date Completed: 20230207 Latest Revision: 20240413
رمز التحديث: 20240413
مُعرف محوري في PubMed: PMC9897518
DOI: 10.1371/journal.pone.0281281
PMID: 36735698
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0281281