Computer algorithm identifies 188 new CRISPR gene editing systems

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Computer algorithm identifies 188 new CRISPR gene editing systems

Computer algorithm identifies 188 new CRISPR gene editing systems

CRISPR systems, powerful tools in genetic engineering, have their limitations. Scientists have now discovered nearly 200 new CRISPR systems in the native habitats of bacteria, some of which can edit human cells more precisely than existing systems.

The CRISPR-Cas9 gene editing tool has been one of the most significant scientific developments in the past decade, with its creators being awarded the Nobel Prize in Chemistry. Scientists use it to efficiently cut and paste edits to human cells, offering the potential for treating various diseases, improving crops, controlling pests, and manipulating bacteria.

The system includes a guide RNA that targets DNA fragments, such as disease-causing DNA, and uses an enzyme (typically Cas9) to cut out the sequence, replacing it with something more beneficial. Recently, alternative Cas9 variants with different characteristics, such as higher precision or larger editing ranges, have been developed.

Now, this family of systems has the potential to expand further. Researchers from the Broad Institute, MIT, and the National Institutes of Health (NIH) used an algorithm to search for new CRISPR systems.

CRISPR is a bacterial self-defense tool in nature, so the research team delved into three bacterial databases from diverse environments like Antarctic lakes, breweries, and dog saliva. In this case, the algorithm was set to find genes related to CRISPR.

Computer algorithm identifies 188 new CRISPR gene editing systems

Within weeks, the system identified thousands of CRISPR systems, including 188 previously unknown ones. In laboratory tests, they demonstrated a range of functions, belonging to both known and novel categories.

Some belong to the I-type CRISPR system, with guide RNA sequences longer than Cas9. This allows them to more precisely target the objective, reducing the risk of off-target editing—a major concern in CRISPR gene editing. Two I-type systems identified in the tests could edit human cells, and their size suggests they could be delivered using the same packaging as currently used for CRISPR-Cas9.

Another I-type system exhibited “collateral activity,” breaking down nucleic acids after binding to the target. This mechanism, previously used in diagnostic tools like SHERLOCK, can identify diseases from samples with only one DNA or RNA molecule.

The study also discovered a VII-type system targeting RNA, opening up a range of new tools through RNA editing. Other systems can be used to record the expression time of certain genes or serve as sensors for cell activity.

This research not only significantly expands the field of possible gene editing tools but also indicates that exploring microbial ecosystems in concealed environments could bring potential benefits to humanity.

Co-first author of the study, Soumya Kannan, stated, “Some of these microbial systems were only found in water from mines. If no one had been interested in this, we might never have seen these systems. Increasing sampling diversity is crucial for continuing to expand the diversity we discover.”

The study was published in the journal “Science.”