Nanoligomers Targeting Human miRNA for the Treatment of Severe COVID-19 Are Safe and Nontoxic in Mice

Colleen R. McCollum, Colleen M. Courtney, Nolan J. O'Connor, Thomas R. Aunins, Yuchen Ding, Tristan X. Jordan, Keegan L. Rogers, Stephen Brindley, Jared M. Brown, Prashant Nagpal, Anushree Chatterjee

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)3087-3106
Number of pages20
JournalACS Biomaterials Science and Engineering
Volume8
Issue number7
DOIs
StatePublished - 11 Jul 2022
Externally publishedYes

Keywords

  • COVID-19
  • antisense therapy
  • biodistribution
  • host immune response
  • safety

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