High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles

Nanoscale
Andrea LongattiNatalie Tigue

Abstract

Exosomes are extracellular vesicles that mediate cell-to-cell communication by transferring biological cargo, such as DNA, RNA and proteins. Through genetic engineering of exosome-producing cells or manipulation of purified exosomes, it is possible to load exosomes with therapeutic molecules and target them to specific cells via the display of targeting moieties on their surface. This provides an opportunity to exploit a naturally-occurring biological process for therapeutic purposes. In this study, we explored the potential of single chain variable fragments (scFv) as targeting domains to achieve delivery of exosomes to cells expressing a cognate antigen. We generated exosomes targeting the Her2 receptor and, by varying the affinity of the scFvs and the Her2 expression level on recipient cells, we determined that both a high-affinity anti-Her2-scFv (KD≤ 1 nM) and cells expressing a high level (≥106 copies per cell) of Her2 were optimally required to enable selective uptake. We also demonstrate that targeting exosomes to cells via a specific cell surface receptor can alter their intracellular trafficking route, providing opportunities to influence the efficiency of delivery and fate of intracellular cargo. These experiments pro...Continue Reading

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Citations

Mar 30, 2019·PloS One·Christina SchindlerNatalie J Tigue
Jun 10, 2020·Future Medicinal Chemistry·Johann Mar Gudbergsson
Mar 21, 2020·Frontiers in Bioengineering and Biotechnology·Jin Xiang WongBernd H A Rehm
Aug 6, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Davod JafariAli Samadikuchaksaraei
Mar 16, 2019·Experimental & Molecular Medicine·Daniel E MurphyPieter Vader
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Dec 3, 2020·International Journal of Nanomedicine·Juntang ShaoYuxian Shen
Dec 19, 2020·Journal of Extracellular Vesicles·Gensheng ZhangZhijian Cai
Feb 15, 2021·Trends in Neurosciences·Dipankar DuttaSteven M Jay
Aug 20, 2019·Seminars in Cancer Biology·Vadim V TarasovGjumrakch Aliev
Feb 21, 2021·Seminars in Cancer Biology·Migara Kavishka JayasingheMinh T N Le
May 4, 2021·Applied Microbiology and Biotechnology·Christoph KeysbergThomas Noll
Jul 15, 2021·Tissue Engineering and Regenerative Medicine·Hojun ChoiChulhee Choi
Sep 19, 2019·Analytical Chemistry·Huixia DiDingbin Liu

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Methods Mentioned

BETA
genetic
transfection
genetic modification
flow cytometry
confocal microscopy
super-resolution microscopy
ELISA
transmission electron microscopy
phage display
FACS

Software Mentioned

Prism
GraphPad
TreeStar
FlowJo
ImageJ
NTA3
Odyssey Image Studio

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