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Guiding protein delivery into live cells using DNA-programmed membrane fusion

Intracellular delivery of proteins provides a direct means to manipulate cell function and probe the intracellular environment. However, direct cytoplasmic delivery of proteins suffers from limited availability of efficient toolsets, and thus remains challenging in research and therapeutic applicati...

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Detalles Bibliográficos
Autores principales: Sun, Lele, Gao, Yanjing, Wang, Yaoguang, Wei, Qin, Shi, Jiye, Chen, Nan, Li, Di, Fan, Chunhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050539/
https://www.ncbi.nlm.nih.gov/pubmed/30079211
http://dx.doi.org/10.1039/c8sc00367j
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author Sun, Lele
Gao, Yanjing
Wang, Yaoguang
Wei, Qin
Shi, Jiye
Chen, Nan
Li, Di
Fan, Chunhai
author_facet Sun, Lele
Gao, Yanjing
Wang, Yaoguang
Wei, Qin
Shi, Jiye
Chen, Nan
Li, Di
Fan, Chunhai
author_sort Sun, Lele
collection PubMed
description Intracellular delivery of proteins provides a direct means to manipulate cell function and probe the intracellular environment. However, direct cytoplasmic delivery of proteins suffers from limited availability of efficient toolsets, and thus remains challenging in research and therapeutic applications. Natural biological cargo delivery processes, like SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex mediated membrane fusion and other vesicle fusion in live cells, enable targeted delivery with high efficiency. A surrogate of SNARE machinery represents a new direction in intracellular protein delivery. Here, we report a DNA-programmed membrane fusion strategy for guiding the efficient intracellular delivery of proteins into live cells. The inherent programmability of DNA hybridization provides spatiotemporal control of the fusion between protein-encapsulated liposomes and cell membranes, enabling rapid release of proteins directly into the cytoplasm, while still remaining functional due to the bypassing of the endosomal trap. We further demonstrate that delivered exogenous Cytochrome c effectively regulates the cell fate. Hence, this DNA-mediated fusion strategy holds great potential for protein drug delivery, regenerative medicine and gene editing.
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spelling pubmed-60505392018-08-03 Guiding protein delivery into live cells using DNA-programmed membrane fusion Sun, Lele Gao, Yanjing Wang, Yaoguang Wei, Qin Shi, Jiye Chen, Nan Li, Di Fan, Chunhai Chem Sci Chemistry Intracellular delivery of proteins provides a direct means to manipulate cell function and probe the intracellular environment. However, direct cytoplasmic delivery of proteins suffers from limited availability of efficient toolsets, and thus remains challenging in research and therapeutic applications. Natural biological cargo delivery processes, like SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex mediated membrane fusion and other vesicle fusion in live cells, enable targeted delivery with high efficiency. A surrogate of SNARE machinery represents a new direction in intracellular protein delivery. Here, we report a DNA-programmed membrane fusion strategy for guiding the efficient intracellular delivery of proteins into live cells. The inherent programmability of DNA hybridization provides spatiotemporal control of the fusion between protein-encapsulated liposomes and cell membranes, enabling rapid release of proteins directly into the cytoplasm, while still remaining functional due to the bypassing of the endosomal trap. We further demonstrate that delivered exogenous Cytochrome c effectively regulates the cell fate. Hence, this DNA-mediated fusion strategy holds great potential for protein drug delivery, regenerative medicine and gene editing. Royal Society of Chemistry 2018-06-15 /pmc/articles/PMC6050539/ /pubmed/30079211 http://dx.doi.org/10.1039/c8sc00367j Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
Sun, Lele
Gao, Yanjing
Wang, Yaoguang
Wei, Qin
Shi, Jiye
Chen, Nan
Li, Di
Fan, Chunhai
Guiding protein delivery into live cells using DNA-programmed membrane fusion
title Guiding protein delivery into live cells using DNA-programmed membrane fusion
title_full Guiding protein delivery into live cells using DNA-programmed membrane fusion
title_fullStr Guiding protein delivery into live cells using DNA-programmed membrane fusion
title_full_unstemmed Guiding protein delivery into live cells using DNA-programmed membrane fusion
title_short Guiding protein delivery into live cells using DNA-programmed membrane fusion
title_sort guiding protein delivery into live cells using dna-programmed membrane fusion
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050539/
https://www.ncbi.nlm.nih.gov/pubmed/30079211
http://dx.doi.org/10.1039/c8sc00367j
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