ARMMs as a versatile platform for intracellular delivery of macromolecules

• DOI: 10.1038/s41467-018-03390-x
• Publication Date: 2018-02-28T10:41:00Z
• Authors: Qiyu Wang; Jiujiu Yu; Tatenda Kadungure; Joseph Beyene; Hong Zhang; Quan Lu
• Keywords: and Biochemical Nutrition; 0301 basic medicine; Arrestins; Science; Recombinant Fusion Proteins; Green Fluorescent Proteins; Other Nutrition; 610; and Tissue Engineering; Article; Extracellular Vesicles; 03 medical and health sciences; Genetic; CRISPR-Associated Protein 9; 616; Animals; Humans; Molecular Biology; Nutrition; Mice, Knockout; Drug Carriers; Molecular engineering; Protein delivery; Q; Molecular; Cell Biology; 3. Good health; HEK293 Cells; A549 Cells; RNA; Cellular; Tumor Suppressor Protein p53; Human and Clinical Nutrition

AbstractMajority 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.