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Excited to share the last preprint from my PhD, 4 years after graduating! @petrsulc.bsky.social's lab embedded protein coding sequences into RNA origami via creative use of paranemic cohesion, allowing us to maximize structure without changing the target sequence. 🧬🧪 www.biorxiv.org/content/10.6...

biorxiv.orgEngineered mRNA nanostructures expand the design space of mRNA therapeutics through programmable protein expression and immune stimulationMessenger RNA (mRNA) therapeutics have transformed vaccination and protein replacement strategies, yet efforts to improve their performance have focused largely on sequence engineering, nucleotide mod...

22/9/26, 6:02 pm2 reposts10 likes

Erik Poppleton

@poppleton.phd

22 Sept

Why do this? LNP-delivered mRNA (e.g vaccines) have a loading problem, you don't get many mRNAs per particle. We wondered if we could deliver more by compacting the mRNA into an origami. It works! The mRNA-origami fold into monodisperse rectangles and encapsulate much better than commercial mRNA.

Erik Poppleton

@poppleton.phd

22 Sept

Lots of purification and controls later to ensure that we transfected fully-structured RNA, we were able to show that cells will express this highly-structured mRNA, albeit at a much lower level than unstructured controls. This appears to be a structurally-mediated, and not activation of the ISR.

Erik Poppleton

@poppleton.phd

22 Sept

In addition to complexing well with LNPs, the origami also survive intact for up to 60 days at fridge temperatures in PBS! What you're going to have to read the paper to find out more about are the immunological outcomes of structuring the mRNA. There's a lot more than fits in a thread!