MIT researchers have discovered a new class of DNA-cutting enzymes, known as Fanzors, in eukaryotic organisms. This breakthrough enhances the capabilities of RNA-guided gene-editing tools and offers more accurate and efficient genome editing options, especially in human cells.
A recent study reveals the widespread presence of RNA-guided enzymes, Fanzors, in various eukaryotic species.
Fanzors, a group of programmable DNA-cutting enzymes found in a diverse range of organisms including snails, algae, and amoebas, have been identified in large numbers by researchers at MIT’s McGovern Institute for Brain Research. Functioning similarly to the bacterial enzymes in CRISPR systems, Fanzors are RNA-guided enzymes that target specific DNA sites. Their discovery, reported in Science Advances, provides a rich pool of programmable enzymes that could be leveraged for scientific and medical purposes.
Omar Abudayyeh and Jonathan Gootenberg, McGovern Fellows, emphasize the importance of RNA-guided tools for ease of use and versatility.
The Role of CRISPR and Fanzors
The application of RNA-guided enzymes, exemplified by the CRISPR system – a defense mechanism in bacteria, demonstrates their laboratory usefulness. Feng Zhang, an MIT professor and McGovern investigator, alongside Abudayyeh and Gootenberg, has transformed DNA modification methods through CRISPR-based tools, expediting research and fostering the development of potential gene therapies.
Amoeba proteus.
Further exploration in the bacterial world has revealed various RNA-guide enzymes, each with unique lab applications. The recent discovery of Fanzors by Zhang’s team marks a novel chapter in RNA-guided biology.
Fanzors are the first RNA-guided enzymes identified in eukaryotes – a group encompassing plants, animals, and fungi, characterized by a membrane-bound nucleus containing genetic material, unlike nucleus-lacking prokaryotes (bacteria).
Gootenberg notes the rich potential in eukaryotic systems for discovering novel tools, distinct from long-studied prokaryotic systems.
Abudayyeh and Gootenberg hope that enzymes naturally evolved in eukaryotes may operate more safely and effectively in eukaryotic cells, including human cells. Zhang’s team has successfully engineered Fanzor enzymes to precisely target specific DNA sequences in human cells.
In their latest research, Abudayyeh and Gootenberg found certain Fanzors can target DNA in human cells effectively even without prior optimization.
Evolutionary Insights and Prospective Applications
Before this study, only hundreds of Fanzors were known among eukaryotes. A comprehensive genetic database search, led by lab member Justin Lim, has now expanded this diversity tenfold.
The team identified over 3,600 Fanzors in eukaryotes and their infecting viruses, classifying them into five distinct families. Comparative analysis of these enzymes provided insights into their extensive evolutionary history.
Fanzors likely evolved from TnpBs, RNA-guided DNA-cutting bacterial enzymes. Their genetic resemblance to TnpBs initially drew attention from Zhang’s group and the team of Gootenberg and Abudayyeh.
The evolutionary study by Gootenberg and Abudayyeh suggests multiple introductions of these bacterial predecessors into eukaryotic cells, possibly through viruses or symbiotic bacteria. Post-adoption by eukaryotes, the enzymes adapted new features, like a signal for entering the cell nucleus to access DNA.
Through experiments by biological engineering graduate student Kaiyi Jiang, the team found that Fanzors evolved a unique DNA-cutting site, enabling more precise targeting than their TnpB ancestors. Certain Fanzors demonstrated 10 to 20 percent efficiency in cutting target sequences in human cell genomes.
Abudayyeh and Gootenberg anticipate the development of advanced genome editing tools from Fanzors, seeing it as a promising new platform with multiple capabilities.
Abudayyeh remarks on the vast potential offered by introducing these RNA-guided systems to the eukaryotic realm.
Reference: “Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses” by Kaiyi Jiang, Justin Lim, Samantha Sgrizzi, Michael Trinh, Alisan Kayabolen, Natalya Yutin, Weidong Bao, Kazuki Kato, Eugene V. Koonin, Jonathan S. Gootenberg and Omar O. Abudayyeh, 27 September 2023, Science Advances.
DOI: 10.1126/sciadv.adk0171
Table of Contents
Frequently Asked Questions (FAQs) about Fanzors gene editing
What are Fanzors and where have they been discovered?
Fanzors are programmable DNA-cutting enzymes discovered by MIT researchers in various eukaryotic organisms, including snails, algae, and amoebas. They are RNA-guided enzymes that can be programmed to target specific DNA sites, similar to bacterial enzymes in CRISPR systems, and they offer significant advancements in the field of gene editing.
How do Fanzors differ from CRISPR?
While CRISPR is a gene-editing tool derived from a bacterial defense system, Fanzors are RNA-guided enzymes found in eukaryotic organisms. Fanzors represent a significant diversification in the field of RNA-guided genome editing, potentially offering more precise and efficient genome modifications, particularly in human cells.
What potential do Fanzors hold for future research and medicine?
Fanzors hold great potential for developing sophisticated genome editing tools. Their natural evolution in eukaryotic organisms might enable them to function more safely and efficiently in eukaryotic cells, including humans. This opens up new possibilities for advanced research and the development of experimental gene therapies.
Who led the research on Fanzors at MIT?
The research on Fanzors at MIT was led by McGovern Fellows Omar Abudayyeh and Jonathan Gootenberg, with significant contributions from their team.
What does the discovery of Fanzors imply for the field of gene editing?
The discovery of Fanzors marks a significant expansion in the diversity of RNA-guided gene-editing tools. It suggests a new frontier in gene editing technology, with the potential for more versatile and precise applications in scientific research and medical treatments.
More about Fanzors gene editing
- MIT McGovern Institute for Brain Research
- Science Advances Journal
- Overview of CRISPR Technology
- RNA-Guided Enzymes Research
- Eukaryotic Organisms and Gene Editing
- Evolution of Gene Editing Tools
- Omar Abudayyeh’s Research Profile
- Jonathan Gootenberg’s Academic Contributions
- Feng Zhang’s Laboratory at MIT
- Developments in Genome Editing Technology
