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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.
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.
Jan 2024 — Dec 2026
$447,730
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