Mar 03 2025
The New TIGR-Tas Gene Editing System
Remember CRISPR (clustered regularly interspaced short palindromic repeats) – that new gene-editing system which is faster and cheaper than anything that came before it? CRISPR is derived from bacterial systems which uses guide RNA to target a specific sequence on a DNA strand. It is coupled with a Cas (CRISPR Associated) protein which can do things like cleave the DNA at the targeted location. We are really just at the beginning of exploring the potential of this new system, in both research and therapeutics.
Well – we may already have something better than CSRISP: TIGR-Tas. This is also an RNA-based system for targeting specific sequences of DNA and delivering a TIGR associated protein to perform a specific function. TIGR (Tandem Interspaced Guide RNA) may have some useful advantages of CRISPR.
As presented in a new paper, TIGR is actually a family of gene editing systems. It was discovered not by happy accident, but by specifically looking for it. As the paper details: “through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain of Cas9”. This means they started with Cas9 and then trolled through the vast database of phage and parasitic bacteria for similar sequences. They found what they were looking for – another family of RNA-guided gene editing systems.
Like CRISPR, TIGR is an RNA guided system, and has a modular structure. Different Tas proteins can be coupled with the TIGR to perform different actions at the targeted site. But there are several potential advantages for TIGR over CRISPR. Like CRISPR it is RNA guided, but TIGR uses both strands of the DNA to find its target sequence. This “dual guided” approach may lead to fewer off-target errors. While CRISPR works very well, there is a trade-off in CRISPR systems between speed and precision. The faster it works, the greater the number of off-target actions – like cleaving the DNA in the wrong place. The hope is that TIGR will make fewer off-target mistakes because of better targeting.