TIGR-Tas (Tandem Interspaced Guide RNA-associated proteins) is a family of RNA-guided DNA-targeting systems discovered in prokaryotes and their viruses. These systems utilize a dual-spacer targeting mechanism, compared to the single spacer required by CRISPR-Cas9-mediated gene targeting.

TIGR-Tas systems were reported in February 2025 by researchers at the Broad Institute of MIT and Harvard and MIT's McGovern Institute for Brain Research.

TIGR-Tas systems were discovered through computational mining approaches that began with structural analysis of the RNA-binding domain of SpCas9. Through iterative structural and sequence homology-based searches, protein were discovered that contain Nop domains—hallmarks of eukaryotic box C/D snoRNA ribonucleoproteins (RNPs)—associated with distinctive tandem interspaced guide RNA arrays.

The discovery process employed advanced computational methods, including protein large language models, to cluster related proteins based on their likely evolutionary relationships. This approach identified more than 20,000 different Tas proteins, predominantly from bacteriophages and parasitic bacteria.

TIGR arrays consist of repetitive sequences organized into dual-repeat units or stem-loop structures. Each unit contains:

TIGR-associated (Tas) proteins are classified into three main types:

TIGR arrays are transcribed and processed into 36-nucleotide guide RNAs called tigRNAs. Processing occurs at precise sites within edge repeats and requires the presence of Tas proteins, though the proteins themselves do not directly catalyze the cleavage.

Unlike CRISPR systems that use a single guide RNA to target one DNA strand, TIGR systems employ a tandem-spacer targeting mechanism: