ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Engineered extracellular vesicles as nanosponges for lysosomal degradation of PCSK9.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Alleviation of diabetic cardiomyopathy via preventing VCAM1-positive cells from senescence by engineered nanovesicles.Journal of nanobiotechnology · 2026Article
- Advances in immune cell-based therapeutic agents for the treatment of inflammation-related diseases.Acta pharmaceutica Sinica. B · 2026Review
- The degradation revolution: harnessing targeted protein degradation for the treatment of human diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Bioengineering of extracellular vesicles with scaffold proteins for drug delivery.Journal of nanobiotechnology · 2026Review
- Surface-modified extracellular vesicles take their chance in the big PCSK9 inhibitors' race.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Klebsiella pneumoniae-derived extracellular vesicles impair endothelial function by inhibiting SIRT1.Cell communication and signaling : CCS · 2025Article
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Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the degradation of the low-density lipoprotein receptor (LDLR), and PCSK9 inhibition emerges as an attractive strategy for atherosclerosis management. In this study, extracellular vesicles (EVs) were engineered to nanosponges, which could efficiently adsorb and deliver PCSK9 into lysosomes for degradation. Briefly, nanosponges were engineered by modifying EVs with EGF-A/PTGFRN fusion protein (PCSK9 binding domain EGF-A from the mutant LDLR with higher affinity was fused to the C terminus of prostaglandin F2 receptor negative regulator). The modification endowed the EVs with hundreds of EGF-As displayed on the surface, and thus the capacity to adsorb PCSK9 efficiently. The adsorbed PCSK9 would thus be delivered into lysosomes for degradation when the nanosponges were endocytosed by liver cells, thus releasing endogenous LDLR from degradation. In the ApoE
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