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10.1016/j.ymthe.2021.05.004

http://scihub22266oqcxt.onion/10.1016/j.ymthe.2021.05.004
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33992805!8118699!33992805
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suck abstract from ncbi


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pmid33992805      Mol+Ther 2021 ; 29 (7): 2219-2226
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  • A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19 #MMPMID33992805
  • Idris A; Davis A; Supramaniam A; Acharya D; Kelly G; Tayyar Y; West N; Zhang P; McMillan CLD; Soemardy C; Ray R; O'Meally D; Scott TA; McMillan NAJ; Morris KV
  • Mol Ther 2021[Jul]; 29 (7): 2219-2226 PMID33992805show ga
  • Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective small interfering RNA (siRNA) therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle (LNP) delivery system. Multiple siRNAs targeting highly conserved regions of the SARS-CoV-2 virus were screened, and three candidate siRNAs emerged that effectively inhibit the virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel LNP formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.
  • |*COVID-19 Drug Treatment[MESH]
  • |Administration, Intravenous[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics[MESH]
  • |Animals[MESH]
  • |COVID-19/metabolism/virology[MESH]
  • |Drug Delivery Systems/*methods[MESH]
  • |Female[MESH]
  • |Gene Silencing[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Lipids/*chemistry[MESH]
  • |Lung/metabolism[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Transgenic[MESH]
  • |Nanoparticles/*chemistry[MESH]
  • |RNA, Double-Stranded/*administration & dosage/genetics[MESH]
  • |RNA, Small Interfering/*administration & dosage/*genetics[MESH]
  • |RNA, Viral/genetics[MESH]
  • |SARS-CoV-2/*genetics[MESH]
  • |Transcriptome/drug effects[MESH]


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