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Review
. 2024 Apr 26;32(2):101259.
doi: 10.1016/j.omtm.2024.101259. eCollection 2024 Jun 13.

Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency

Charlotte A René  1   2   3 , Robin J Parks  1   2   3   4
Affiliations
Review

Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency

Charlotte A René et al. Mol Ther Methods Clin Dev. .

Abstract

Extracellular vesicles (EVs) have the innate ability to carry proteins, lipids, and nucleic acids between cells, and thus these vesicles have gained much attention as potential therapeutic delivery vehicles. Many strategies have been explored to enhance the loading of specific cargoes of interest into EVs, which could result in the delivery of more therapeutic to recipient cells, thus enhancing therapeutic efficacy. In this review, we discuss the natural biogenesis of EVs, the mechanism by which proteins and nucleic acids are selected for inclusion in EVs, and novel methods that have been employed to enhance loading of specific cargoes into EVs. As well, we discuss biodistribution of administered EVs in vivo and summarize clinical trials that have attempted to harness the therapeutic potential of EVs.

Keywords: biodistribution; bioengineering; exosomes; extracellular vesicles; therapeutic delivery.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Biogenesis of exosomes and microvesicles Invagination of the plasma membrane of the cell leads to development of the early endosome. The early endosome matures into the MVB, at which point Rab5 is replaced by Rab7. In ESCRT-dependent exosome biogenesis, ESCRT-0 interacts with Ub-proteins and binds PtdIns3P on the membrane of the endosome. ESCRT-I and ESCRT-II are then recruited, driving the invagination of the endosomal membrane. ESCRT-III completes ILV formation and is dissociated by Vps4. In ESCRT-independent exosome biogenesis, ILV formation can be driven by Rab31, CD63, or through the syndecan-syntenin-ALIX pathway. In both types of biogenesis, the MVB fuses with the cell membrane and leads to the release of ILV as exosomes. In microvesicle biogenesis, outward budding of the cell membrane and pinching off of the membrane results in the release of microvesicles. This process involves ARF1 and ARF6. ESCRT, endosomal sorting complex required for transport; ILV, intraluminal vesicle; MVB, multivesicular body; PtdIns3, phosphoinositide; Rab, ras-associated GTPases; Ub, ubiquinated.
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