The CRISPR system is a powerful tool for genetic engineering, but it also has its limitations. Now, scientists have discovered nearly 200 new CRISPR systems in the bacteria's native habitat and found that some of them can edit human cells more precisely than existing systems.
The CRISPR-Cas9 gene-editing tool is one of the most important scientific developments of the past decade, earning its discoverer the Nobel Prize in Chemistry. Scientists can use it to perform efficient cut-and-paste editing of human cells, potentially treating a wide range of diseases, as well as improving crops, controlling pests and manipulating bacteria.
The system involves a guide RNA that targets a segment of DNA, such as a disease-causing one, and then uses an enzyme (usually Cas9) to cut out the sequence and replace it with something more beneficial. More recently, Cas9 alternatives have been developed with additional properties, including greater precision or greater editing scope.
Now, the family has the potential to get even bigger. Researchers at the Broad Institute, MIT and the National Institutes of Health (NIH) used an algorithm to find new CRISPR systems. In nature, CRISPR is a self-defense tool used by bacteria, so the team dug into three databases of bacteria found in environments as diverse as Antarctic lakes, wineries and dog saliva. In this case, the team set the algorithm to look for genes associated with CRISPR.
Within weeks, the system identified thousands of CRISPR systems, including 188 previously unknown to science. In lab tests, they demonstrated a range of capabilities that fall into both known and entirely new categories.
Several of them are type I CRISPR systems, and their guide RNA sequences are longer than Cas9. This means they can be targeted more precisely, reducing the risk of off-target editing - one of the main issues with CRISPR gene editing. In testing, two of the Type I systems were found to be capable of editing human cells, and their size should allow them to be delivered in the same packaging currently used for CRISPR-Cas9.
Another type I system displays so-called "collateral activity", which breaks down the nucleic acid after binding to the target. This mechanism has previously been used in diagnostic tools (such as SHERLOCK) to identify diseases from samples with just one DNA or RNA molecule.
The research also identified a type VII system for RNA that could unlock a range of new tools through RNA editing. Other systems can be used to record the timing of expression of certain genes, or as sensors of cellular activity.
This research not only greatly expands the field of possible gene editing tools, but also shows that exploring microbial ecosystems in cryptic environments could bring potential benefits to humans.
Soumya Kannan, co-first author of the study, said: "Some of these microbial systems have only been found in coal mine water. If it weren't for someone's interest, we might never have seen these systems. Expanding the sampling diversity is very important to continue to expand the diversity we find."
The research was published in the journal Science.