# CRISPR screens for SARS-CoV-2 Host Factors

> **NIH NIH R21** · BROAD INSTITUTE, INC. · 2020 · $440,000

## Abstract

PROJECT SUMMARY
In collaboration with Dr. Wilen (Yale University) and Dr. Goujon (CNRS, France), we will establish cell line
models and conduct genome-wide CRISPR screens to identify host genes that are necessary for SARS-CoV-2
infection. We will first use Vero cells from the African Green Monkey, as they are a well-established model for
many pathogens, and we had previously generated a genome-wide library for this species. Preliminary data
suggest that we have also generated human cell lines that can serve as effective model systems, and these
screens will be conducted as soon as the models are sufficiently validated. Across these screens, we expect to
find host factors that are necessary for infection, such as the surface binding target for the virus, ACE2, and
anticipate that the screens will identify additional genes that, when knocked out, prevent viral cytopathic
effects. Additionally, we can modulate the selective pressure to identify factors that, when lost, sensitize the
cells to SARS-CoV-2, which will provide a complementary view into host cell biology. Likewise, we will also
conduct CRISPR activation screens to identify host genes that, when overexpressed, provide protection
against infection, which may identify restriction factors that the virus must overcome. Primary screens will be
validated with secondary pools, which will also allow for testing of genes across more conditions and cell types,
establishing the generalizability of the results. Finally, combinatorial screens will be conducted to generate
unbiased genetic interaction maps of hit genes, which can identify redundancies that are partially masked in a
primary screen, as well as unexpected synergies across pathways. Focused, mechanistic follow-up of genes
identified by these screens is outside the scope of this proposal, but is of immediate interest to the Wilen and
Goujon groups.

## Key facts

- **NIH application ID:** 10163544
- **Project number:** 1R21AI157835-01
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** John Gerard Doench
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2020-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163544

## Citation

> US National Institutes of Health, RePORTER application 10163544, CRISPR screens for SARS-CoV-2 Host Factors (1R21AI157835-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163544. Licensed CC0.

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