Generation of Chimeric RNA with Type III CRISPR-Cas

Patent Status

Patent Pending

Brief Description

RNA editing enables safe, reversible, and dose-tunable genetic correction without the permanent genomic risks or cargo limits of traditional DNA editing. However, conventional RNA editing tools often lack the ability to perform precise, large-scale modifications or site specific cut and paste operations on transcripts, which limits their therapeutic and research utility. 

UC Berkeley researchers have developed a programmable RNA editing platform that utilizes Type III CRISPR-Cas complexes integrated with a ligase to generate chimeric RNA molecules. This method enables robust RNA trans splicing, allowing for the replacement of defective exons, the insertion of large genetic sequences into transcripts, and the creation of novel fusion proteins. This approach provides a transient and potentially safer method for correcting genetic errors at the transcript level while offering greater flexibility for large scale RNA engineering.

Suggested uses

• RNA level correction of genetic mutations by replacing defective exons through trans splicing.
• Generation of novel chimeric proteins and fusion transcripts for research and therapeutic discovery.
• Large scale RNA engineering to introduce functional domains or regulatory elements into specific transcripts.
• Development of transient therapies for diseases caused by large gene defects such as muscular dystrophies.
• Programmable modification of viral RNAs to inhibit replication or alter viral function.

Advantages

• Uses programmable Csm complexes for surgical, site-specific RNA cleavage.
• Enables insertion of large sequences, bypassing the cargo limits of traditional gene editing.
• Integrates nuclease and ligase functions to streamline the production of stable chimeric transcripts.
• Operates at the RNA level, eliminating the risk of permanent, off-target genomic changes.