Reducible Branched Ester-Amine Quadpolymers (rBEAQs) Codelivering Plasmid DNA and RNA Oligonucleotides Enable CRISPR/Cas9 Genome Editing

Yuan Rui, David R. Wilson, Katie Sanders, Jordan Green

Research output: Contribution to journalArticle

Abstract

Functional codelivery of plasmid DNA and RNA oligonucleotides in the same nanoparticle system is challenging due to differences in their physical properties as well as their intracellular locations of function. In this study, we synthesized a series of reducible branched ester-amine quadpolymers (rBEAQs) and investigated their ability to coencapsulate and deliver DNA plasmids and RNA oligos. The rBEAQs are designed to leverage polymer branching, reducibility, and hydrophobicity to successfully cocomplex DNA and RNA in nanoparticles at low polymer to nucleic acid w/w ratios and enable high delivery efficiency. We validate the synthesis of this new class of biodegradable polymers, characterize the self-assembled nanoparticles that these polymers form with diverse nucleic acids, and demonstrate that the nanoparticles enable safe, effective, and efficient DNA-siRNA codelivery as well as nonviral CRISPR-mediated gene editing utilizing Cas9 DNA and sgRNA codelivery.

Original languageEnglish (US)
Pages (from-to)10472-10480
Number of pages9
JournalACS Applied Materials and Interfaces
Volume11
Issue number11
DOIs
StatePublished - Mar 20 2019

Keywords

  • codelivery
  • CRISPR
  • DNA
  • nanoparticle
  • nonviral
  • rBEAQs
  • reducible branched ester-amine quadpolymers
  • RNA oligonucleotides

ASJC Scopus subject areas

  • Materials Science(all)

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