Site-directed RNA editing by harnessing ADARs: advances and challenges

Adenosine deaminase acting on RNA (ADAR) enzyme–mediated A-to-I RNA editing is widely distributed in the transcriptome. It plays an important role in autoimmune surveillance, tumorigenesis, and development. Recently, several site-directed RNA editing (SDRE) systems have been developed to target disease causative point mutations by flexibly exploiting the catalytic adenosine deamination properties of ADARs. This is based on the fact that A-to-I RNA editing is essentially an adenosine-guanine transition. In contrast to genome editing, RNA editing is tunable and transient, and there are still some shortcomings that need to be addressed. Here, we outline several SDRE systems that rely on the catalytic deamination activity of endogenous or exogenous ADARs, attempting to illustrate their strategies and discuss numerous shortcomings that need to be overcome in the future. Graphical abstract