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Last Updated: 02/08/2024

Defining the role of ADAR1 and RNA editing in protection from infectious disease

Objectives

Using a mouse model, this project will define the role of ADAR1 and RNA editing in protection from malaria and investigate if this protection is also applicable to other infectious diseases.

Principal Investigators / Focal Persons

Mary Anne O’Connell

Rationale and Abstract

Editing of RNA by ADAR1 is essential to prevent activation of immune responses by endogenous ‘self’ RNA. Particularly, ADAR1 prevents activation of cytosolic dsRNA sensors, including RLRs, PKR, and OAS-RNAse L, which typically respond to viral (or other ‘non-self’) RNA. Currently, there is significant interest in developing inhibitors of ADAR1 as a therapeutic approach to activate these immune response pathways, as recent publications have shown that targeting ADAR1 can drive effective cancer immunotherapy. However, whether ADAR1 can also be targeted to provide protection from infectious diseases has not been widely considered. Preliminary data show that targeting ADAR1 can provide significant protection against malaria. This suggests that ADAR1 inhibitors may be effective in treatment of a range of both viral and non-viral infectious diseases.

Thematic Categories

Basic Science

Date

Jan 2024 — Dec 2026

Total Project Funding

$447,730

Funding Details
Czech Science Foundation (GACR), Czech Republic

Grant ID: GA24-12635S
CZK 9.82M
Project Site

Czech Republic

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