Bait-and-Switch Supramolecular Strategy to Generate Noncationic RNA-Polymer Complexes for RNA Delivery

Ziwen Jiang, Wei Cui, Priyaa Prasad, Mollie A. Touve, Nathan C. Gianneschi, Jesse Mager*, S. Thayumanavan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


RNA interference (RNAi) requires the intracellular delivery of RNA molecules to initiate the neutralization of targeted mRNA molecules, inhibiting the expression or translation of the targeted gene. Current polymers and lipids that are used to deliver RNA molecules are generally required to be positively charged, to achieve complexation with RNA and the cellular internalization. However, positive surface charge has been implicated as the reason for toxicity in many of these systems. Herein, we report a novel strategy to generate noncationic RNA-polymer complexes for RNA delivery with low cytotoxicity. We use an in situ electrostatic complexation using a methylated pyridinium group, which is simultaneously removed during the RNA binding step. The resultant complexes demonstrate successful knockdown in preimplantation mammalian embryos, thus providing a new approach for nucleic acid delivery.

Original languageEnglish (US)
Pages (from-to)435-442
Number of pages8
Issue number1
StatePublished - Jan 14 2019

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


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