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  Programmable Extracellular Vesicles for Macromolecule Delivery and Genome Modifications

Zhang, X., Xu, Q., Zi, Z., Liu, Z., Wan, C., Crisman, L., et al. (2020). Programmable Extracellular Vesicles for Macromolecule Delivery and Genome Modifications. Developmental Cell, 55, 1-18. doi:10.1016/j.devcel.2020.11.007.

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 Creators:
Zhang, Xiaojuan , Author
Xu, Quanbin, Author
Zi, Zhike1, Author              
Liu, Zeyu, Author
Wan, Chun, Author
Crisman, Lauren , Author
Shen, Jingshi, Author
Liu, Xuedong, Author
Affiliations:
1Cell Signaling Dynamics (Zhike Zi), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117284              

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Free keywords: VSV-G exosomes Gectosomes split GFP macromolecule delivery PINK1 PCSK9 genome editing mass spectrometry mathematical modeling
 Abstract: Getting large macromolecules through the plasma membrane and endosomal barriers remains a major challenge. Here, we report a generalizable method of delivering proteins and ribonucleoproteins (RNPs) to cells in vitro and mouse liver tissue in vivo with engineered ectosomes. These ectosomes, referred to as “Gectosomes,” are designed to co-encapsulate vesicular stomatitis virus G protein (VSV-G) with bioactive macromolecules via split GFP complementation. We found that this method enables active cargo loading, improves the specific activity of cargo delivery, and facilitates Gectosome purification. Experimental and mathematical modeling analyses suggest that active cargo loading reduces non-specific encapsulation of cellular proteins, particularly nucleic-acid-binding proteins. Using Gectosomes that encapsulate Cre, Ago2, and SaCas9, we demonstrate their ability to execute designed modifications of endogenous genes in cell lines in vitro and mouse liver tissue in vivo, paving the way toward applications of this technology for the treatment of a wide range of human diseases.

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Language(s): eng - English
 Dates: 2020-12-082020-12-21
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.devcel.2020.11.007
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Title: Developmental Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 55 Sequence Number: - Start / End Page: 1 - 18 Identifier: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134