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

ACS Applied Materials & Interfaces
Yuan RuiJordan J Green

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.

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Citations

Jul 4, 2019·Current Gene Therapy·Cia-Hin Lau, Chung Tin
Oct 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·T J ThomasC K S Pillai
Apr 5, 2020·Advanced Drug Delivery Reviews·Franziska Freitag, Ernst Wagner
Nov 3, 2020·Clinical and Translational Medicine·Hengji ZhanYuchen Liu
Jun 16, 2021·The Journal of Clinical Investigation·Jing ZhangAkrit Sodhi
Jan 20, 2021·ACS Biomaterials Science & Engineering·Denis RoutkevitchJordan J Green
Jul 30, 2019·ACS Applied Materials & Interfaces·Weijie YeFu-Jian Xu
Jun 8, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jayoung KimJordan J Green
Jan 11, 2022·Advanced Healthcare Materials·Erin W Kavanagh, Jordan J Green
Jan 19, 2022·ACS Applied Bio Materials·Akbar HasanzadehMichael R Hamblin
Feb 2, 2022·Biomaterials Science·Yi LinUlrich Lächelt

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