Unlocking the Power of Gene Editing: New Systems Discovered
Introduction
Scientists at MIT’s McGovern Institute for Brain Research and the Broad Institute of MIT and Harvard have made a groundbreaking discovery, finding ancient systems with potential to expand the genome editing toolbox. These systems, called TIGR (Tandem Interspaced Guide RNA) systems, use RNA to guide them to specific sites on DNA. TIGR systems can be reprogrammed to target any DNA sequence of interest, and they have distinct functional modules that can act on the targeted DNA.
How TIGR Systems Work
TIGR systems use RNA to guide them to specific sites on DNA. The RNA-binding component of the protein interacts with an RNA guide that directs it to a specific site in the genome. Some TIGR proteins can cut the DNA at that site, using an adjacent DNA-cutting segment of the protein. This modularity could facilitate tool development, allowing researchers to swap useful new features into natural TIGR proteins.
Advantages of TIGR Systems
TIGR systems have several advantages over other RNA-guided systems, such as CRISPR. They are more compact, with a quarter of the size of Cas9 on average, making them easier to deliver. This could overcome a major obstacle to therapeutic deployment of gene editing tools. Additionally, TIGR systems do not require the presence of PAMs (protospacer adjacent motifs), which are required for CRISPR systems. This means that any site in the genome can be targeted.
Discovery and Testing
The researchers used an iterative process to search for proteins with similar structural features to the CRISPR-Cas9 protein. They began by zeroing in on a structural feature of the CRISPR-Cas9 protein that binds to the enzyme’s RNA guide. They then searched hundreds of millions of biological proteins with known or predicted structures, looking for any that shared a similar domain. The team used an artificial intelligence language model to cluster the proteins they had found into groups according to their likely evolutionary relationships.
Conclusion
The discovery of TIGR systems has the potential to revolutionize the field of gene editing. With their ability to target any site in the genome and their compact size, TIGR systems could be used to develop new and more precise gene editing tools. The researchers are excited to investigate the natural role of TIGR systems in viruses and how they can be adapted for research or therapeutics.
Frequently Asked Questions
Q: How do TIGR systems work?
A: TIGR systems use RNA to guide them to specific sites on DNA. The RNA-binding component of the protein interacts with an RNA guide that directs it to a specific site in the genome.
Q: What are the advantages of TIGR systems?
A: TIGR systems are more compact, with a quarter of the size of Cas9 on average, making them easier to deliver. They also do not require the presence of PAMs, which are required for CRISPR systems.
Q: How were TIGR systems discovered?
A: The researchers used an iterative process to search for proteins with similar structural features to the CRISPR-Cas9 protein. They began by zeroing in on a structural feature of the CRISPR-Cas9 protein that binds to the enzyme’s RNA guide.
