Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles

Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Nanjing University researchers report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. The researchers show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. They demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. They found that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. The researchers believe that their bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.

Schematic of anti-GPC3 scoff and engineered fusogen
co-expressing eFT-CNVs for cytosolic delivery of therapeutics

Fig. 1

Intrinsic GPC3 and B2M are knocked out using CRISPR/Cas 9 followed by co-expressing anti-GPC3 scFv and engineered fusogen on HEK293 cell membranes. The eFT-CNVs are generated by mechanical extrusion of the donor cells and loaded with various drugs, e.g., nucleic acids, protein toxins, or chemotherapeutic agents, for on-target cytosolic delivery.

Wang L, Wang G, Mao W, Chen Y, Rahman MM, Zhu C, Prisinzano PM, Kong B, Wang J, Lee LP, Wan Y. (2023) Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles. Nat Commun 14(1):3366. [article]

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