气候变化领域集成服务门户(CCPortal): Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism

CCPortal

DOI	10.1073/PNAS.2016860117
	Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism
	van Bruggen C.; Punihaole D.; Keith A.R.; Schmitz A.J.; Tolar J.; Frontiera R.R.; Reineke T.M.
发表日期	2021
ISSN	00278424
起始页码	32919
结束页码	32928
卷号	117 期号:52
英文摘要	Polymeric vehicles that efficiently package and controllably release nucleic acids enable the development of safer and more efficacious strategies in genetic and polynucleotide therapies. Developing delivery platforms that endogenously monitor the molecular interactions, which facilitate binding and release of nucleic acids in cells, would aid in the rational design of more effective vectors for clinical applications. Here, we report the facile synthesis of a copolymer containing quinine and 2-hydroxyethyl acrylate that effectively compacts plasmid DNA (pDNA) through electrostatic binding and intercalation. This polymer system poly(quinine-co-HEA) packages pDNA and shows exceptional cellular internalization, transgene expression, and low cytotoxicity compared to commercial controls for several human cell lines, including HeLa, HEK 293T, K562, and keratinocytes (N/TERTs). Using quinine as an endogenous reporter for pDNA intercalation, Raman imaging revealed that proteins inside cells facilitate the unpackaging of polymer–DNA complexes (polyplexes) and the release of their cargo. Our work showcases the ability of this quinine copolymer reporter to not only facilitate effective gene delivery but also enable diagnostic monitoring of polymer–pDNA binding interactions on the molecular scale via Raman imaging. The use of Raman chemical imaging in the field of gene delivery yields unprecedented insight into the unpackaging behavior of polyplexes in cells and provides a methodology to assess and design more efficient delivery vehicles for gene-based therapies. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Biomaterial; Drug delivery; Gene editing; Gene therapy; Polymer
语种	英语
scopus关键词	2-hydroxyethyl acrylate; acrylic acid derivative; quinine; cell culture; chemistry; gene transfer; genetics; HEK293 cell line; HeLa cell line; human; K-562 cell line; plasmid; Acrylates; Cells, Cultured; Gene Transfer Techniques; HEK293 Cells; HeLa Cells; Humans; K562 Cells; Plasmids; Quinine
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179643
作者单位	Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, United States; Department of Pediatrics, Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, United States; Department of Chemistry, University of Vermont, Burlington, VT 05405, United States
推荐引用方式 GB/T 7714	van Bruggen C.,Punihaole D.,Keith A.R.,et al. Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism[J],2021,117(52).
APA	van Bruggen C..,Punihaole D..,Keith A.R..,Schmitz A.J..,Tolar J..,...&Reineke T.M..(2021).Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	van Bruggen C.,et al."Quinine copolymer reporters promote efficient intracellular DNA delivery and illuminate a protein-induced unpackaging mechanism".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).