Evitar: designing anti-viral RNA therapies against future RNA viruses

Dingyao Zhang1,2, Jingru Tian1,2, Yadong Wang1,2,3

  • 1Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA.

Abstract

Insights

We developed Evitar, a pipeline for designing RNA therapeutics like siRNAs and CRISPR guide RNAs against emerging viruses. Evitar can predict effective therapeutics for future outbreaks, accelerating pandemic response.

Area of Science:

  • Virology
  • Bioinformatics
  • RNA Therapeutics

Background:

  • Emerging RNA viruses pose significant threats, as demonstrated by the COVID-19 pandemic.
  • Current therapeutic options for novel RNA viruses are limited, highlighting the need for rapid development tools.

Purpose of the Study:

  • To develop a computational pipeline (Evitar) for designing RNA-targeting therapeutics (siRNAs and CRISPR Cas13a gRNAs) against emerging RNA viruses.
  • To enable pre-outbreak design of therapeutics for potential future viral threats.

Main Methods:

  • Developed the Evitar pipeline incorporating Greedy Algorithm with Redundancy and Similarity-weighted Greedy Algorithm with Redundancy.
  • Utilized historical coronavirus genomes for pre-outbreak siRNA and gRNA design simulations.
  • Validated designed siRNAs through in vitro reporter assays against SARS-CoV-2 sequences.

Main Results:

  • Evitar successfully identified potential SARS-CoV-2 targeting siRNAs and CRISPR Cas13a gRNAs using genomic data predating the COVID-19 outbreak.
  • Pre-outbreak therapeutic designs were feasible for MERS-CoV and 2009-H1N1 swine flu viruses.
  • In vitro assays confirmed the ability of designed siRNAs to suppress SARS-CoV-2 viral sequences.

Conclusions:

  • The Evitar pipeline is effective for designing anti-viral siRNAs and gRNAs against future RNA viruses.
  • Propose creating a collection of pre-designed, off-the-shelf siRNA/CRISPR therapeutics to expedite responses to future viral outbreaks.

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