programmed death-ligand 1-targeted extracellular vesicles carrying herpes simplex virus thymidine kinase mRNA

Programmed death-ligand 1-targeted extracellular vesicles carrying herpes simplex virus thymidine kinase mRNA is an experimental cancer therapy that utilizes engineered extracellular vesicles (EVs) to deliver a suicide gene selectively to tumor cells. The EVs, derived from HEK 293FT cells, are loaded with mRNA encoding the herpes simplex virus thymidine kinase (HSV-TK) and functionalized with a PD-L1-binding peptide (CVRARTR) via click chemistry. This targeting strategy ensures that the EVs are preferentially internalized by PD-L1-overexpressing cancer cells. Once inside the cell, the HSV-TK mRNA is translated into the thymidine kinase enzyme, which then converts the prodrug ganciclovir (GCV) into its toxic triphosphate form. This metabolite interferes with DNA replication, leading to selective cell death in the targeted tumor population while sparing normal cells with low PD-L1 expression. Preclinical evidence in MDA-MB-231 breast cancer models has shown significant anti-tumor activity following systemic administration.

Other names

PD-L1-targeted EVs carrying HSV-TK mRNAPD-L-1-targeted EVs carrying HSV-TK mRNAPD-L 1-targeted EVs carrying HSV-TK mRNAPD-L1-targeted extracellular vesicles containing HSV-TK mRNAPD-L-1-targeted extracellular vesicles containing HSV-TK mRNAPD-L 1-targeted extracellular vesicles containing HSV-TK mRNA