188 Types of “New CRISPR Systems” Updated | Genetics – genetics

Scientists at the McGovern Institute for Brain Research, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health (NIH) developed a new search algorithm that made it possible to identify “188 types of new CRISPR.” identify systems [1] », rare in bacterial genomes, includes “thousands of individual systems”. This work was published in the journal Science [2].

Explore databases

Microbial sequence databases contain a “mine of information” about enzymes and other molecules that could be suitable for biotechnology. But these databases have become so large in recent years that it has become difficult to “effectively” search for interesting enzymes.

The team used their algorithm called Fast Locality-Sensitive Hashing-based Clustering (FLSHclust) to search three large public databases containing data on a variety of “unusual” bacteria, including those found in coal mines, breweries, Antarctic lakes, and even Dog saliva is found in lakes.

There, scientists discovered a “surprising” number and variety of CRISPR systems, including systems that can alter the DNA of human cells, others that can target RNA, and many other systems with a variety of other functions.

Interesting faculties

The new systems could potentially be used to engineer mammalian cells with fewer off-target effects than current Cas9 systems [3]. They could one day also be used for diagnostics [4].

Researchers also discovered new mechanisms of action for some CRISPR systems, as well as a system that “precisely” targets RNA and could be used for RNA editing. Other systems could be used as tools to indicate when a gene was expressed or as “sensors of specific activity” in a living cell.

The scientists say their research highlights an “unprecedented level” of diversity and flexibility of CRISPR systems and that it is “likely” that as databases expand, many more rare systems remain to be discovered. Additionally, their algorithm could be used to “discover new genes.”

[1] CRISPR stands for “clustered regularly interspaced short palindromic repeats” and is “a bacterial defense system” that has been integrated into many genome editing and diagnostic tools.

[2] Uncovering the functional diversity of rare CRISPR-Cas systems with deep terascale clustering, Han Altae-Tan et al., Science, November 23, 2023, Volume 382, ​​Issue 6673, DOI: 10.1126/science.adi1910

[3] The researchers discovered several new “variants of known type I CRISPR systems” that use a 32 base pair guide RNA instead of the 20 nucleotides of Cas9. Because of their longer guide RNAs, these systems “could potentially be used to develop gene editing technology that is more precise and less susceptible to off-target editing.” They showed that two of these systems make “small changes” in DNA human cells can do. Because these systems are similar in size to CRISPR-Cas9, they could “probably” be delivered to animal or human cells using the same technologies used for CRISPR today.

[4] One of the Type I systems also showed “collateral activity,” meaning “widespread nucleic acid degradation” after the CRISPR protein bound to its target. Scientists have used similar systems to diagnose infectious diseases, such as SHERLOCK, a tool that can “rapidly” detect a single DNA or RNA molecule.

Source: MIT News, Allessandra DiCoratto (11/23/2023)