Extracellular vesicles as a platform for membrane-associated therapeutic protein delivery

J Extracell Vesicles. 2018 Mar 1;7(1):1440131. doi: 10.1080/20013078.2018.1440131. eCollection 2018.

Abstract

Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state-of-the-art of extracellular vesicle (exosome and small-sized microvesicle)-based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.

Keywords: Exosomes; Extracellular vesicle; Membrane protein; Microdomain; Protein therapeutics.

Publication types

  • Review

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (Grant Numbers 2017R1A2B2010292 and 2017R1A3B1023418), the KU-KIST Graduate School of Converging Science and Technology Program, and the KIST Young Fellow Program; Korea Institute of Science and Technology [KIST Young Fellow Program];National Research Foundation of Korea [Grant Number 2017R1A2B2010292];National Research Foundation of Korea [Grant Number 2017R1A3B1023418];KU-KIST Graduate School [Converging Science and Technology Program];