Molecular Components and Trafficking of ARRDC1-Mediated Microvesicles(ARMMs)

The ability to efficiently package and deliver therapeutic molecules to target cells and tissues in diseased individuals remains starkly elusive. Among the many exacerbations that occur with treatment, administered therapeutic cargos often suffer from poor permeability, high toxicity, and often evoke dangerous autoimmune responses. We have recently discovered novel small vesicles known as ARMMs (ARRDC1-Mediated Microvesicles) that are naturally secreted by mammalian cells. We have found that ARMMs exhibit several important features that make them suitable for delivery of biological therapeutics: 1) ARMMs can be readily produced by overexpression of the ARRDC1 protein and are relatively uniform in size (average ~100 nm), 2) specific protein molecules are actively recruited into ARMMs and are protected by the lipid bilayer from degradation, and 3) ARMMs can deliver bioactive cargos into recipient cells. In addition, ARMMs likely elicit little immunogenic response as they are produced by human cells endogenously and can be found in circulating blood.

I have shown that ARMMs can efficiently package and functionally deliver diverse payloads (tumor suppressor protein p53, GFP and p53 RNAs, and the CRISPRCas9/guide RNA complex) into cultured recipient cells, however key questions remain about the endogenous molecular components of ARMMs and the mechanisms of ARMMs uptake into recipient cells. Elucidating these aspects of ARMMs trafficking are paramount to understanding their function and utility as a vehicle for the delivery of biological therapeutic medicines.