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Nanoligomers Targeting Human miRNA for the Treatment of Severe COVID-19 Are Safe and Nontoxic in Mice.
McCollum, Colleen R; Courtney, Colleen M; O'Connor, Nolan J; Aunins, Thomas R; Ding, Yuchen; Jordan, Tristan X; Rogers, Keegan L; Brindley, Stephen; Brown, Jared M; Nagpal, Prashant; Chatterjee, Anushree.
  • McCollum CR; Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
  • Courtney CM; Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
  • O'Connor NJ; Sachi Bioworks, Inc., 685 S Arthur Ave Unit 5, Colorado Technology Center, Louisville, Colorado 80027, United States.
  • Aunins TR; Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
  • Ding Y; Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
  • Jordan TX; Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, United States.
  • Rogers KL; Department of Microbiology, New York University Langone, New York, New York 10016, United States.
  • Brindley S; Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
  • Brown JM; Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
  • Nagpal P; Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
  • Chatterjee A; Sachi Bioworks, Inc., 685 S Arthur Ave Unit 5, Colorado Technology Center, Louisville, Colorado 80027, United States.
ACS Biomater Sci Eng ; 8(7): 3087-3106, 2022 07 11.
Article in English | MEDLINE | ID: covidwho-1900423
ABSTRACT
The devastating effects of the coronavirus disease 2019 (COVID-19) pandemic have made clear a global necessity for antiviral strategies. Most fatalities associated with infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result at least partially from uncontrolled host immune response. Here, we use an antisense compound targeting a previously identified microRNA (miRNA) linked to severe cases of COVID-19. The compound binds specifically to the miRNA in question, miR-2392, which is produced by human cells in several disease states. The safety and biodistribution of this compound were tested in a mouse model via intranasal, intraperitoneal, and intravenous administration. The compound did not cause any toxic responses in mice based on measured parameters, including body weight, serum biomarkers for inflammation, and organ histopathology. No immunogenicity from the compound was observed with any administration route. Intranasal administration resulted in excellent and rapid biodistribution to the lungs, the main site of infection for SARS-CoV-2. Pharmacokinetic and biodistribution studies reveal delivery to different organs, including lungs, liver, kidneys, and spleen. The compound was largely cleared through the kidneys and excreted via the urine, with no accumulation observed in first-pass organs. The compound is concluded to be a safe potential antiviral treatment for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: MicroRNAs / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: ACS Biomater Sci Eng Year: 2022 Document Type: Article Affiliation country: Acsbiomaterials.2c00510

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Full text: Available Collection: International databases Database: MEDLINE Main subject: MicroRNAs / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: ACS Biomater Sci Eng Year: 2022 Document Type: Article Affiliation country: Acsbiomaterials.2c00510