Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery

细胞外小泡 配体(生物化学) 化学 小泡 细胞生物学 计算机科学 人机交互 生物物理学 纳米技术 材料科学 生物 生物化学 受体
作者
Alena Ivanova,Lukas Badertscher,Gwen O’Driscoll,Joakim Bergman,Euan Gordon,Anders Gunnarsson,Camilla Johansson,Michael J. Munson,Cristiana Spinelli,Sara Torstensson,Liisa Vilén,Andrei Voirel,John Wiseman,Janusz Rak,Niek Dekker,Elisa Lázaro-Ibáñez
出处
期刊:Advanced Science [Wiley]
卷期号:10 (34) 被引量:1
标识
DOI:10.1002/advs.202304389
摘要

Efficient and targeted delivery of therapeutic agents remains a bottleneck in modern medicine. Here, biochemical engineering approaches to advance the repurposing of extracellular vesicles (EVs) as drug delivery vehicles are explored. Targeting ligands such as the sugar GalNAc are displayed on the surface of EVs using a HaloTag-fused to a protein anchor that is enriched on engineered EVs. These EVs are successfully targeted to human primary hepatocytes. In addition, the authors are able to decorate EVs with an antibody that recognizes a GLP1 cell surface receptor by using an Fc and Fab region binding moiety fused to an anchor protein, and they show that this improves EV targeting to cells that overexpress the receptor. The authors also use two different protein-engineering approaches to improve the loading of Cre recombinase into the EV lumen and demonstrate that functional Cre protein is delivered into cells in the presence of chloroquine, an endosomal escape enhancer. Lastly, engineered EVs are well tolerated upon intravenous injection into mice without detectable signs of liver toxicity. Collectively, the data show that EVs can be engineered to improve cargo loading and specific cell targeting, which will aid their transformation into tailored drug delivery vehicles.
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