2023-08-10 ニューサウスウェールズ大学(UNSW)
◆siRNAは、ワクチンに使用されるmRNAよりもはるかに小さなRNAの一種で、ウイルスを含む遺伝子のタンパク質産生を妨害します。
◆この研究では、siRNA療法がSARS-CoV-2の複製を効果的に防ぐことが示され、全ての懸念される変異種に対して99.9%のウイルスレベルの低下を示しました。また、SotrovimabおよびRemdesivirよりも強力であり、免疫系が機能しなくても効果があるため、免疫が低下している人々にとって重要な治療選択肢となることが期待されています。
◆現在はマウスモデルでの前臨床研究の最適化と評価が次のステップとなりますが、将来的には臨床試験に進展する可能性があります。
<関連情報>
- https://newsroom.unsw.edu.au/news/health/universal-sirna-covid-19-treatment-shows-promise-lab
- https://www.sciencedirect.com/science/article/pii/S0166354223001559
新規siRNA治療薬がSARS-CoV-2に対して多バリアント有効性を示す Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2
Ellen Bowden-Reid, Scott Ledger, Yuan Zhang, Francesca Di Giallonardo, Anupriya Aggarwal, Alberto Ospina Stella, Anouschka Akerman, Vanessa Milogiannakis, Gregory Walker, William Rawlinson, Stuart Turville, Anthony D. Kelleher, Chantelle Ahlenstiel
Antiviral Research Available online: 20 July 2023
DOI:https://doi.org/10.1016/j.antiviral.2023.105677
Highlights
•Short interfering (si)RNA were designed to target human and animal SARS-CoV-1/2 genomes.
•Multiple siRNA displayed potent antiviral effect in various in vitro assays.
•Broad-spectrum antiviral effect was observed in SARS-CoV-2 variants of concern.
•These antiviral siRNA have potential as a pan-SARS-coronavirus treatment.
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed individuals who lack robust immune responses following vaccination, and others at risk for severe COVID and long-COVID. RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics and a high genetic barrier to antiviral escape. Here we describe novel siRNAs, targeting highly conserved regions of the SARS-CoV-1 and 2 genome of both human and animal species, with multi-variant antiviral potency against eight SARS-CoV-2 lineages – Ancestral VIC01, Alpha, Beta, Gamma, Delta, Zeta, Kappa and Omicron. Treatment with our siRNA resulted in significant protection against virus-mediated cell death in vitro, with >97% cell survival (P < 0.0001), and corresponding reductions of viral nucleocapsid RNA of up to 99.9% (P < 0.0001). When compared to antivirals; Sotrovimab and Remdesivir, the siRNAs demonstrated a more potent antiviral effect and similarly, when multiplexing siRNAs to target different viral regions simultaneously, an increased antiviral effect was observed compared to individual siRNA treatments (P < 0.0001). These results demonstrate the potential for a highly effective broad-spectrum direct acting antiviral against multiple SARS-CoV-2 variants, including variants resistant to antivirals and vaccine generated neutralizing antibodies.
