Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing.

Autor:	Rui Y; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Wilson DR; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Choi J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Varanasi M; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sanders K; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Karlsson J; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Lim M; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Green JJ; Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Departments of Ophthalmology, Materials Science and Engineering, and Chemical and Biomolecular Engineering, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2019 Dec 06; Vol. 5 (12), pp. eaay3255. Date of Electronic Publication: 2019 Dec 06 (Print Publication: 2019).
DOI:	10.1126/sciadv.aay3255
Abstrakt:	Efficient cytosolic protein delivery is necessary to fully realize the potential of protein therapeutics. Current methods of protein delivery often suffer from low serum tolerance and limited in vivo efficacy. Here, we report the synthesis and validation of a previously unreported class of carboxylated branched poly(β-amino ester)s that can self-assemble into nanoparticles for efficient intracellular delivery of a variety of different proteins. In vitro, nanoparticles enabled rapid cellular uptake, efficient endosomal escape, and functional cytosolic protein release into cells in media containing 10% serum. Moreover, nanoparticles encapsulating CRISPR-Cas9 ribonucleoproteins (RNPs) induced robust levels of gene knock-in (4%) and gene knockout (>75%) in several cell types. A single intracranial administration of nanoparticles delivering a low RNP dose (3.5 pmol) induced robust gene editing in mice bearing engineered orthotopic murine glioma tumors. This self-assembled polymeric nanocarrier system enables a versatile protein delivery and gene editing platform for biological research and therapeutic applications. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze:	MEDLINE
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