ADAR-Mediated RNA Editing and Its Therapeutic Potentials

Adenosine-to-inosine (A-to-I) RNA editing mediated by the ADAR (adenosine deaminase acting on RNA) protein family is the primary type of epitranscriptomic modification known to occur in mammal cells. Recently, several technologies have been developed to re-target this RNA modification to desired locations within specific transcripts. This possibility opened a scenario in which targeted RNA-base editing tools can be used as therapeutic strategies to correct mutations at the RNA level. The chapter will go into detail about the therapeutic potentials of these different RNA base-editing technologies, after providing a brief overview of the roles and functions of ADAR family members. The chapter aims to review the recent advancements of targeted RNA-base editing methodologies and their translation to therapeutic settings. We will discuss strategies leveraging exogenous and endogenous ADAR to create a wholesome perspective on the potential of this molecular mechanism as a tool to correct disease-causing G-to-A point mutations. In this context, clinically relevant approaches and their potential future applications, as well as their currently challenging limitations, will be evaluated.