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Programmable RNA cleavage using DNA-­induced silencing complex, DISC

College
College of Arts & Sciences
Researchers
Nakanishi, Kotaro
Dayeh, Daniel "Danny"
Licensing Manager
Dahlman, Jason "Jay"
614/292-7945
dahlman.3@osu.edu

TS-037307 — This technology can be used to make programmable RNA restriction enzymes using guide DNA strands.

The need for programmable, affordable RNA-cleaving restriction enzymes has resulted in high demand for the development of new technology. Conventional approaches such as artificial endonucleases recognize and cleave RNA targets, but are limited by high production costs. Reducing these costs is dif…

The Need

The need for programmable, affordable RNA-cleaving restriction enzymes has resulted in high demand for the development of new technology. Conventional approaches such as artificial endonucleases recognize and cleave RNA targets, but are limited by high production costs. Reducing these costs is difficult due to the technology’s dependence on the endonuclease’s recognition motifs that must be reprogrammed for each new target sequence. In DNA-cleaving proteins, this dependence was overcome by the development of Cas9 systems that use guide-RNAs to recognize targets without requiring changes to the protein. However, the RNA-equivalent (RCas9) remains expensive and technically demanding due to its dependence on large, unstable guide-RNAs. Further, RCas9 requires the presence of the PAM sequence motif at the target site in order to cleave the target RNA. This requirement limits the number of possible targets for a given RNA sequence, which restricts application of the technology. Therefore, the biotechnology market would benefit from a technology that both minimizes the costs associated with current RNA-cleaving technology and also expands its utility.

The Technology

Dr. Nakanishi and his collaborators at The Ohio State University have created a technology for RNA cleavage called the DNA-induced Slicer Complex (DISC) system that uses an Argonaute-family protein loaded with a DNA guide. The primary advantage of the DISC system over other RNA cleavage systems is DISC’s use of DNA as a guiding sequence rather than RNA. Relative to RNA, the increased stability and lower cost of DNA enables users to increase the scale and throughput of experiments. Also, DISC requires shorter guide sequences than RCas9’s RNA guides, which further lowers the cost of production. Additionally, DISC is not limited by the PAM motifs required by Cas9-based endonuclease systems, allowing unrestricted access to RNA targets of interest. Therefore, DISC provides a cost-reducing RNA-cleavage system that expands the range of use beyond what is currently available in nucleic acid-guided endonuclease technology.

Commercial Applications

  • Targeted cleavage of RNAs in both research and clinical settings

Benefits/Advantages

  • Cost-reducing method of cleaving RNA polynucleotides
  • Increases the range of use beyond that of Cas9 technologies