ARMMs as a versatile platform for intracellular delivery of macromolecules

Qiyu Wang, Jiujiu Yu, Tatenda Kadungure, Joseph Beyene, Hong Zhang, Quan Lu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number960
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Macromolecules
macromolecules
delivery
platforms
Product Packaging
Clustered Regularly Interspaced Short Palindromic Repeats
Guide RNA
Intracellular Space
RNA Editing
Arrestin
Tumor Suppressor Protein p53
Aptitude
packaging
Social Responsibility
tumor suppressor proteins
Packaging
DNA Damage
Tissue
Therapeutics
editing

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

ARMMs as a versatile platform for intracellular delivery of macromolecules. / Wang, Qiyu; Yu, Jiujiu; Kadungure, Tatenda; Beyene, Joseph; Zhang, Hong; Lu, Quan.

In: Nature communications, Vol. 9, No. 1, 960, 01.12.2018.

Research output: Contribution to journalArticle

Wang, Qiyu ; Yu, Jiujiu ; Kadungure, Tatenda ; Beyene, Joseph ; Zhang, Hong ; Lu, Quan. / ARMMs as a versatile platform for intracellular delivery of macromolecules. In: Nature communications. 2018 ; Vol. 9, No. 1.
@article{d2d71b0e6f004ebb85b2fdd70c115895,
title = "ARMMs as a versatile platform for intracellular delivery of macromolecules",
abstract = "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.",
author = "Qiyu Wang and Jiujiu Yu and Tatenda Kadungure and Joseph Beyene and Hong Zhang and Quan Lu",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-018-03390-x",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - ARMMs as a versatile platform for intracellular delivery of macromolecules

AU - Wang, Qiyu

AU - Yu, Jiujiu

AU - Kadungure, Tatenda

AU - Beyene, Joseph

AU - Zhang, Hong

AU - Lu, Quan

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85043266526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043266526&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03390-x

DO - 10.1038/s41467-018-03390-x

M3 - Article

C2 - 29511190

AN - SCOPUS:85043266526

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 960

ER -