TY - JOUR AU - Yu, Lifang AU - Marchisio, Mario Andrea PY - 2020 M3 - Review TI - Types I and V Anti-CRISPR Proteins: From Phage Defense to Eukaryotic Synthetic Gene Circuits JO - Frontiers in Bioengineering and Biotechnology UR - https://www.frontiersin.org/articles/10.3389/fbioe.2020.575393 VL - 8 SN - 2296-4185 N2 - Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins), a prokaryotic RNA-mediated adaptive immune system, has been repurposed for gene editing and synthetic gene circuit construction both in bacterial and eukaryotic cells. In the last years, the emergence of the anti-CRISPR proteins (Acrs), which are natural OFF-switches for CRISPR-Cas, has provided a new means to control CRISPR-Cas activity and promoted a further development of CRISPR-Cas-based biotechnological toolkits. In this review, we focus on type I and type V-A anti-CRISPR proteins. We first narrate Acrs discovery and analyze their inhibitory mechanisms from a structural perspective. Then, we describe their applications in gene editing and transcription regulation. Finally, we discuss the potential future usage—and corresponding possible challenges—of these two kinds of anti-CRISPR proteins in eukaryotic synthetic gene circuits. ER -