Cargando…

ARMMs as a versatile platform for intracellular delivery of macromolecules

Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic t...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Qiyu, Yu, Jiujiu, Kadungure, Tatenda, Beyene, Joseph, Zhang, Hong, Lu, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840177/
https://www.ncbi.nlm.nih.gov/pubmed/29511190
http://dx.doi.org/10.1038/s41467-018-03390-x
_version_ 1783304522495426560
author Wang, Qiyu
Yu, Jiujiu
Kadungure, Tatenda
Beyene, Joseph
Zhang, Hong
Lu, Quan
author_facet Wang, Qiyu
Yu, Jiujiu
Kadungure, Tatenda
Beyene, Joseph
Zhang, Hong
Lu, Quan
author_sort Wang, Qiyu
collection PubMed
description Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex. We demonstrate selective recruitment of these macromolecules into ARMMs. When delivered intracellularly via ARMMs, these macromolecules are biologically active in recipient cells. P53 delivered via ARMMs induces DNA damage-dependent apoptosis in multiple tissues in mice. Together, our results provide proof-of-principle demonstration that ARMMs represent a highly versatile platform for packaging and intracellular delivery of therapeutic macromolecules.
format Online
Article
Text
id pubmed-5840177
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-58401772018-03-09 ARMMs as a versatile platform for intracellular delivery of macromolecules Wang, Qiyu Yu, Jiujiu Kadungure, Tatenda Beyene, Joseph Zhang, Hong Lu, Quan Nat Commun Article Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex. We demonstrate selective recruitment of these macromolecules into ARMMs. When delivered intracellularly via ARMMs, these macromolecules are biologically active in recipient cells. P53 delivered via ARMMs induces DNA damage-dependent apoptosis in multiple tissues in mice. Together, our results provide proof-of-principle demonstration that ARMMs represent a highly versatile platform for packaging and intracellular delivery of therapeutic macromolecules. Nature Publishing Group UK 2018-03-06 /pmc/articles/PMC5840177/ /pubmed/29511190 http://dx.doi.org/10.1038/s41467-018-03390-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Qiyu
Yu, Jiujiu
Kadungure, Tatenda
Beyene, Joseph
Zhang, Hong
Lu, Quan
ARMMs as a versatile platform for intracellular delivery of macromolecules
title ARMMs as a versatile platform for intracellular delivery of macromolecules
title_full ARMMs as a versatile platform for intracellular delivery of macromolecules
title_fullStr ARMMs as a versatile platform for intracellular delivery of macromolecules
title_full_unstemmed ARMMs as a versatile platform for intracellular delivery of macromolecules
title_short ARMMs as a versatile platform for intracellular delivery of macromolecules
title_sort armms as a versatile platform for intracellular delivery of macromolecules
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840177/
https://www.ncbi.nlm.nih.gov/pubmed/29511190
http://dx.doi.org/10.1038/s41467-018-03390-x
work_keys_str_mv AT wangqiyu armmsasaversatileplatformforintracellulardeliveryofmacromolecules
AT yujiujiu armmsasaversatileplatformforintracellulardeliveryofmacromolecules
AT kadunguretatenda armmsasaversatileplatformforintracellulardeliveryofmacromolecules
AT beyenejoseph armmsasaversatileplatformforintracellulardeliveryofmacromolecules
AT zhanghong armmsasaversatileplatformforintracellulardeliveryofmacromolecules
AT luquan armmsasaversatileplatformforintracellulardeliveryofmacromolecules