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Compact CRISPR alternative uses bacterial proteins to insert large DNA segments
Confirmed
In Short: Cornell researchers have created a compact gene-editing system that can insert large DNA segments into bacteria, potentially useful for plants, animals, and humans.
Cornell researchers have developed a smaller gene-editing system that can insert large DNA segments into bacteria, an early result they hope to adapt for use in plants, animals, and humans. The system, detailed in a report on October 7, 2026, uses bacterial proteins to achieve precise DNA insertion.
The new system, which is smaller than many CRISPR-Cas systems, relies on a protein called TldR that uses an RNA guide to locate the intended site in a genome. Another protein, TniQ, helps orient the DNA payload correctly.
The researchers engineered this non-CRISPR system by combining bacterial components that do not naturally occur together, creating a tool that could be more efficient and accurate than existing methods.
According to Cornell, the system is currently tested only in bacteria, but the team is examining a broader family of proteins related to TldR for potential use in human or plant cells.
Jill Banfield, a UC Berkeley professor, noted that the discovery of these compact CRISPR systems in uncultivable bacteria opens new possibilities for gene editing. The systems were found by scanning metagenome databases over the past 15 years.
Jennifer Doudna, a UC Berkeley professor and Howard Hughes Medical Institute investigator, emphasized the importance of finding these systems in a major branch of the bacterial tree, which could lead to a whole new world of microbes.
The team's approach involves identifying new large proteins in proximity to a CRISPR array and universal Cas proteins, but not part of any known system, expanding the gene-editing toolbox available to researchers and physicians.
The compact nature of these systems, befitting their presence in some of the smallest life forms on the planet, could make them easier to insert into cells for DNA editing.
The discovery nearly doubles the number of simple and compact CRISPR-Cas systems potentially useful as laboratory and biomedical tools, highlighting the ongoing evolution of gene-editing technology.
The researchers are still testing related proteins to find versions that might work beyond bacteria, with the goal of adapting the system for broader applications.
What this adds
The research adds to the growing body of work on compact CRISPR alternatives, potentially offering more efficient and accurate gene editing options.
What's confirmed
- Cornell researchers have developed a smaller gene-editing system that can insert large DNA segments into bacteria, an early result they hope to adapt for use in plants, animals, and humans. The system, detailed in a report on October 7, 2026, uses bacterial proteins to achieve precise DNA insertion.
- The new system, which is smaller than many CRISPR-Cas systems, relies on a protein called TldR that uses an RNA guide to locate the intended site in a genome. Another protein, TniQ, helps orient the DNA payload correctly.
- The researchers engineered this non-CRISPR system by combining bacterial components that do not naturally occur together, creating a tool that could be more efficient and accurate than existing methods.
- According to Cornell, the system is currently tested only in bacteria, but the team is examining a broader family of proteins related to TldR for potential use in human or plant cells.
- Jill Banfield, a UC Berkeley professor, noted that the discovery of these compact CRISPR systems in uncultivable bacteria opens new possibilities for gene editing. The systems were found by scanning metagenome databases over the past 15 years.
- Jennifer Doudna, a UC Berkeley professor and Howard Hughes Medical Institute investigator, emphasized the importance of finding these systems in a major branch of the bacterial tree, which could lead to a whole new world of microbes.
- The team's approach involves identifying new large proteins in proximity to a CRISPR array and universal Cas proteins, but not part of any known system, expanding the gene-editing toolbox available to researchers and physicians.
- The compact nature of these systems, befitting their presence in some of the smallest life forms on the planet, could make them easier to insert into cells for DNA editing.
- The discovery nearly doubles the number of simple and compact CRISPR-Cas systems potentially useful as laboratory and biomedical tools, highlighting the ongoing evolution of gene-editing technology.
- The researchers are still testing related proteins to find versions that might work beyond bacteria, with the goal of adapting the system for broader applications.
What's still developing
- Inserting a much larger stretch of DNA at a precise location is harder, and placement at the wrong site can create complications.
- “These are particularly interesting because the key protein in these CRISPR systems is approximately the same as Cas9, but is not Cas9. It is part of a minimal system that has obvious potential for gene editing,” said Jill Banfield, a UC Berkeley professor of earth and planetary sciences and of environmental science, policy and management.
- The variety of uncultivable bacteria has only recently been recognized, in large part due to Banfield and her lab colleagues, who use metagenomic analysis to explore microbial diversity in exotic environments, from toxic pools in abandoned mines to the soil in Superfund contamination cleanup sites and the guts of premature infants.
- The two groups of nanoarchaea found to contain CRISPR-Cas9 were first described by Banfield from acid mine drainage.
- The CRISPR system was discovered in bacteria several decades ago, and many biologists worldwide have contributed to understanding its function.
- “We used sensitive models we created for all known CRISPR-associated or Cas proteins to identify new large proteins that are in proximity to a CRISPR array and universal Cas proteins, but not part of any known system,” said post-doctoral fellow David Burstein, one of three first authors.
- The majority of all bacterial life on the planet is basically unknown because these organisms cannot be cultivated in lab dishes, probably because they are symbionts and rely upon other microbes for nutrients needed to survive.
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- Because the team was looking for CRISPR systems that use a single effector protein so they would be smaller in size, they looked for microbial genomes lacking accessory proteins used by some CRISPR systems in bacteria.