Kadin T. Crosby

Abstract Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging.

Abstract Selectively eradicating target cells on the basis of their genetic or transcriptional identity remains important in basic research, medicine, biotechnology and agriculture1,2,3. For applications involving bacteria, CRISPR nucleases offer promising options due to their ability to enact RNA-guided counterselection4,5,6,7; however, using these same nucleases for counterselection in eukaryotes has proven much more restrictive8,9,10,11,12,13,14.

Abstract In all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity1,2,3,4,5. Here we report Cas12a3 effector nucleases from type V CRISPR–Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA.