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New Reversible Uridine Modification Chemistry For Labeling and Functionalizing Native Nucleic Acids

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SUMMARY

A chemical process that enables reversible, covalent RNA modification-highly selective for uridine enabling diverse functional group attachment, facilitating nucleic acid labeling

The Unmet Need: Reversible labeling of native RNA in a sequence-independent and membrane-selective manner

 

  • The study of RNA is crucial for understanding fundamental biological processes, from gene expression regulation to disease mechanisms. Accurately probing RNA structure, function, and localization within complex cellular environments, including membrane-associated compartments, requires robust and versatile labeling techniques. There is a significant need for methods that can modify native RNA post-transcriptionally, without requiring genetic manipulation or pre-labeling, to enable real-time analysis and functional studies in diverse biological contexts.

 

  • The study of RNA is crucial for understanding fundamental biological processes, from gene expression regulation to disease mechanisms. Accurately probing RNA structure, function, and localization within complex cellular environments, including membrane-associated compartments, requires robust and versatile labeling techniques. There is a significant need for methods that can modify native RNA post-transcriptionally, without requiring genetic manipulation or pre-labeling, to enable real-time analysis and functional studies in diverse biological contexts.

The Proposed Solution: Posttranscriptional and reversible nucleic acid labeling method, enabling on-demand modifications

 

  • The faculty inventor developed a novel chemical method, called Reversible Uridine Nitrilium-mediated Addition (RUNA), for selectively modifying native RNA with uridine-specific labeling. Unlike many existing RNA labeling techniques, RUNA offers complete reversibility, allowing the native RNA to be recovered after modification. It enables post-transcriptional labeling of RNA in aqueous solutions, avoiding the need for pre-labeling. Furthermore, its modularity permits a wide array of functional group introductions, and critically, it can differentiate between internal and membrane-associated nucleic acids by controlling aldehyde permeability, a capability not readily available with other methods. 

ADVANTAGES

ADVANTAGES

  • Enables reversible and stable covalent labeling of native RNA
  • Offers high selectivity for uridine and single-stranded RNA
  • Allows modular introduction of diverse functional groups (e.g., click handles, dyes, biotin)
  • Provides tunable membrane permeability for selective labeling of compartmentalized RNA

APPLICATIONS

  • Reversible RNA labeling

  • RNA diagnostic probe development

  • Targeted RNA drug delivery

  • Exosome surface RNA analysis