Researchers at MIT, Harvard, and the National Institutes of Health have utilized a new search algorithm to identify 188 different types of rare CRISPR systems in bacterial genomes. This data holds potential to advance genome-editing technology, enabling more precise treatments and diagnostics.
The algorithm, developed in the lab of prominent CRISPR researcher, Professor Feng Zhang uses big-data clustering approaches to scan the vast volumes of genomic data. It is known as Fast Locality-Sensitive Hashing-based clustering (FLSHclust).
The team mined three extensive public databases comprised of data from a multitude of unique bacteria, including those found in breweries, coal mines, Australian lakes, and canine saliva. The results showed an unexpected number and variety of CRISPR systems, including some that could modify DNA in human cells, others that could target RNA, and several with other functions.
These systems could help further refine mammalian cell editing by minimising off-target impacts associated with current Cas9 systems. They may also be useful for diagnostic purposes or to trace cellular activities. Zhang suggests that the vast biodiversity contains undiscovered molecular resources, underscoring the need for improved tools such as FLSHclust.
Flashing a spotlight on the staggering diversity and adaptability of CRISPR, the researchers found thousands of CRISPR systems that fell into new categories. Amongst these, they found variants of Type I CRISPR systems, which use a 32 base pair guide RNA, rather than the 20-nucleotide guide of Cas9, hinting on possible improvements to genetic editing precision and minimising off-target editing. They also found new mechanisms for certain Type IV CRISPR systems and a Type VII system that targets RNA specifically, which could be applied in RNA editing or used as recording or sensing tools within a living cell.
The team believes their algorithm can be used by anyone keen in making sense of large databases to understand protein evolution or to discover new genes. These findings not only demonstrate the tremendous variety CRISPR systems possess, but also how rare most are, found in unusual bacteria. Understanding the diversity and potential these systems hold could revolutionise the way we study molecular biology.
This work was supported by the Howard Hughes Medical Institute, the K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center at MIT and Broad Institute among others. The findings were published in Science.
