Engineered deaminases as a key component of DNA and RNA editing tools

Mol Ther Nucleic Acids. 2023 Oct 20:34:102062. doi: 10.1016/j.omtn.2023.102062. eCollection 2023 Dec 12.

Abstract

Over recent years, zinc-dependent deaminases have attracted increasing interest as key components of nucleic acid editing tools that can generate point mutations at specific sites in either DNA or RNA by combining a targeting module (such as a catalytically impaired CRISPR-Cas component) and an effector module (most often a deaminase). Deaminase-based molecular tools are already being utilized in a wide spectrum of therapeutic and research applications; however, their medical and biotechnological potential seems to be much greater. Recent reports indicate that the further development of nucleic acid editing systems depends largely on our ability to engineer the substrate specificity and catalytic activity of the editors themselves. In this review, we summarize the current trends and achievements in deaminase engineering. The presented data indicate that the potential of these enzymes has not yet been fully revealed or understood. Several examples show that even relatively minor changes in the structure of deaminases can give them completely new and unique properties.

Keywords: ADAR; AID/APOBEC; CRISPR-Cas technology; DNA/RNA editing; MT: RNA/DNA Editing; adenosine deaminase; base editing; cytidine deaminase; protein engineering.

Publication types

  • Review