Carboxylated branched poly(β-amino ester) nanoparticles enable robust intracellular protein delivery and crispr/cas9 gene editing

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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Statement of Purpose: Direct intracellular delivery of protein drugs to target cells is safer than plasmid delivery as it eliminates risks of insertional mutagenesis. In the context of gene editing, there is the added benefit that delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) reduces the probability of off-target editing by reducing RNP persistence time. However, intracellular protein delivery faces many challenges as the large size and hydrophilicity of proteins make them generally membrane impermeable. Poly(β-amino ester)s (PBAEs) are biodegradable, cationic polymers that self-assemble into nanoparticles with nucleic acids via electrostatic interactions and have been developed for effective nucleic acid delivery. In contrast to nucleic acids, different proteins carry different surface charges and nanoparticle encapsulation cannot rely solely on charge interactions. In this study, we modified branched PBAEs with amino acid-like carboxylate ligands and examined their ability to enable intracellular protein delivery. We hypothesized that the carboxylate end-caps facilitate protein encapsulation through hydrogen bonding and salt bridges while the PBAE polymer backbone can enable endosomal escape, resulting in a versatile protein delivery platform.

Original languageEnglish (US)
Title of host publicationSociety for Biomaterials Annual Meeting and Exposition 2019
Subtitle of host publicationThe Pinnacle of Biomaterials Innovation and Excellence - Transactions of the 42nd Annual Meeting
PublisherSociety for Biomaterials
Number of pages1
ISBN (Electronic)9781510883901
StatePublished - Jan 1 2019
Event42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - Seattle, United States
Duration: Apr 3 2019Apr 6 2019

Publication series

NameTransactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium
Volume40
ISSN (Print)1526-7547

Conference

Conference42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence
CountryUnited States
CitySeattle
Period4/3/194/6/19

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Biotechnology
  • Biomaterials
  • Materials Chemistry

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  • Cite this

    Rui, Y., Wilson, D. R., Sanders, K., & Green, J. (2019). Carboxylated branched poly(β-amino ester) nanoparticles enable robust intracellular protein delivery and crispr/cas9 gene editing. In Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - Transactions of the 42nd Annual Meeting (Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium; Vol. 40). Society for Biomaterials.