دورية أكاديمية
Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19.
| العنوان: | Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19. |
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| المؤلفون: | McCollum CR; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States., Courtney CM; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States.; Sachi Bio, Colorado Technology Center, Louisville, Colorado 80027, United States., O'Connor NJ; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States., Aunins TR; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States., Jordan TX; Department of Microbiology, New York University Langone, New York, New York 10016, United States., Rogers KL; Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, 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; Sachi Bio, Colorado Technology Center, Louisville, Colorado 80027, United States.; Antimicrobial Regeneration Consortium Labs, Louisville, Colorado 80027, United States., Chatterjee A; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States.; Sachi Bio, Colorado Technology Center, Louisville, Colorado 80027, United States.; Antimicrobial Regeneration Consortium Labs, Louisville, Colorado 80027, United States. |
| المصدر: | ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2023 Mar 13; Vol. 9 (3), pp. 1656-1671. Date of Electronic Publication: 2023 Feb 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101654670 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-9878 (Electronic) Linking ISSN: 23739878 NLM ISO Abbreviation: ACS Biomater Sci Eng Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, [2015]- |
| مواضيع طبية MeSH: | SARS-CoV-2*/drug effects , SARS-CoV-2*/genetics , COVID-19*/virology , COVID-19 Drug Treatment*/adverse effects , COVID-19 Drug Treatment*/methods , Nanostructures*/administration & dosage , Nanostructures*/adverse effects , Nanostructures*/therapeutic use , Nanomedicine*/methods , Peptide Nucleic Acids*/administration & dosage , Peptide Nucleic Acids*/adverse effects , Peptide Nucleic Acids*/pharmacokinetics , Peptide Nucleic Acids*/therapeutic use , Oligoribonucleotides*/administration & dosage , Oligoribonucleotides*/adverse effects , Oligoribonucleotides*/pharmacokinetics , Oligoribonucleotides*/therapeutic use , Genome, Viral*/drug effects , Genome, Viral*/genetics, Patient Safety ; Animals ; Mice ; Mice, Inbred BALB C ; In Vitro Techniques ; Tissue Distribution |
| مستخلص: | As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro . Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound K |
| فهرسة مساهمة: | Keywords: COVID-19; RNA-dependent RNA polymerase; antisense therapy; biodistribution; safety |
| المشرفين على المادة: | 0 (Peptide Nucleic Acids) 0 (SBCoV202) 0 (Oligoribonucleotides) |
| SCR Organism: | SARS-CoV-2 variants |
| تواريخ الأحداث: | Date Created: 20230228 Date Completed: 20230327 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| DOI: | 10.1021/acsbiomaterials.2c00669 |
| PMID: | 36853144 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2373-9878 |
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| DOI: | 10.1021/acsbiomaterials.2c00669 |