Extracellular vesicle-based protein and RNA delivery

Int J Pharm. 2025 Dec 25:686:126300. doi: 10.1016/j.ijpharm.2025.126300. Epub 2025 Oct 24.

Abstract

The field of protein and RNA therapies has revolutionized the treatment of numerous diseases with the regulatory approval of diverse products during the past few decades. However, the application of protein and RNA therapies has consistently faced significant challenges that substantially impact their safety, stability, bioavailability, and therapeutic efficacy. Consequently, the development of efficient delivery platforms is paramount to amplifying their therapeutic effect and broadening their clinical application. To date, a wide range of nanocarriers have been developed and made great progresses in the field. Extracellular vesicles (EVs) have emerged as a terrific arsenal for designing protein and RNA delivery platforms, due to several beneficial properties. In addition to low immunogenicity and excellent safety, EVs are naturally occurring protein and RNA delivery vehicles with intrinsic ability to protect cargoes from degradation and good membrane permeability. This review delves into the latest advances in EV-based protein and RNA delivery systems with focus on various endogenous and exogenous engineering approaches. Furthermore, this document provides a discussion on the application of EV-based protein and RNA therapies in diseases, as well as the advancements in clinical research related to these therapies.

Keywords: Delivery systems; Extracellular vesicles; Proteins; RNAs; Therapeutics; Vaccines.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Extracellular Vesicles* / metabolism
  • Humans
  • Nanoparticles
  • Proteins* / administration & dosage
  • RNA* / administration & dosage

Substances

  • RNA
  • Proteins
  • Drug Carriers