Advancements in RNA targeting and editing technology

January 31, 2023

Source: X





The new work from Arc Institute, led by graduate student Sita Chandrasekaran and undergrad Cyrus Tau, in collaboration with Patrick Hsu and Silvana Konermann, marks a significant advancement in RNA targeting and editing technology.

• In the context of RNA delivery and therapeutics, the team aimed to directly "write" RNA molecules into messenger RNA (mRNA) to either replace disease-causing exons or engineer synthetic proteins.
• Building on previous work on Cas13d-based RNA targeting, the team developed a groundbreaking technology named RESPLICE. This technology enables fully programmable and highly efficient transcriptome engineering, with reported efficiency rates ranging from 45% to 90%.
• The researchers invented two RNA editing modules utilizing orthogonal RNA-targeting effectors:
  
  
  
  Trans-splicing RNA, which was recruited by the previously discovered Cas13d;
• Cis-splicing interference complex (CIM), promoted by Cas7-11.
• This innovative approach resulted in a significant efficiency boost, approximately 20 times more efficient than conventional methods.
• The team demonstrated the effectiveness of their approach by achieving efficient, specific, and programmable trans-splicing of multi-kilobase RNA cargo into nine endogenous transcripts across two human cell types.
• This research holds immense promise in the fields of RNA therapeutics and molecular biology. By enabling precise manipulation of RNA transcripts, RESPLICE opens up new possibilities for treating genetic disorders, engineering proteins, and advancing our understanding of gene regulation mechanisms.
• The development of RESPLICE and its successful application in editing endogenous RNA transcripts pave the way for further advancements in RNA-based therapies and molecular engineering.

This breakthrough could lead to the development of novel treatments for a wide range of diseases, offering hope for patients with genetic disorders and other conditions that currently lack effective therapeutic options.





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