Understanding RNA Higher-Order Structure Dynamics For CRISPR Applications

A recent publication in Analytical Chemistry details a novel approach to characterizing the higher order structure (HOS) of oligonucleotide therapeutics, a critical factor influencing their function. The study, conducted by researchers from Genentech and RedShiftBio, addresses the limitations of traditional methods by employing a combination of size-exclusion chromatography (SEC) and microfluidic modulation spectroscopy (MMS).

The research focused on characterizing guide RNA (gRNA) aggregates, essential components of the CRISPR-Cas9 gene editing process. By using isothermal and thermal MMS in conjunction with thermal SEC, the scientists were able to monitor real-time HOS changes and observe distinct steps in the thermal dissociation of RNA aggregates. This innovative approach provides valuable insights into RNA structure and dynamics, with potential applications in optimizing RNA therapeutics and formulations.

Read further to explore how this combined methodology can enhance your understanding of RNA higher order structure.