Targeting human exosomes via bispecific antibody platform
Explore the potential of targeting human exosomes using a bispecific antibody platform, enhancing drug delivery capabilities. The study delves into engineering exosomes as drug carriers, developing exosome targeting antibodies (ExTAbs), and verifying exosome delivery efficiency. Future directions include cell-specific delivery verification, functional cargo delivery, and exploring new targeting strategies.
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Targeting human exosomes via bispecific antibody platform Kaitlyn Pierpont, Boya Zhang, Sachith Vidanapathirana, Colin Greineder
Exosomes are natures messengers Herrmann, I.K., et al.. Nat. Nanotechnol. (2021).
Engineering exosomes as drug carriers Our Solution Genetic Engineering Chemical Conjugation Requires genetic modification of parental cells May alter exosome structure Requires reproducible chemistry
Exosome Targeting Antibodies (ExTAbs) Anti-CD63 IgG CD63 CD9 CD81 + 2 affinity ligands
ExTAb structure and characterization VH VL IgG 2:1 2:2 Protein Ladder NR R scFv
ExTAb structure and characterization Kd = 4.4 nM Kd = 2.1 nM Kd = 1.1 nM
Exosome purification and decoration CD63-GFP exosomes
Verification of exosome delivery Wildtype ICAM expressing ICAM expressing Cell only Targeted exosomes + wildtype cells Untargeted exosomes + ICAM cells Targeted exosomes + ICAM cells
Verification of exosome delivery cell only Cell only Untargeted exosomes + cells Targeted exosomes + cells Mouse endothelial cells (bEND3)
In vivo specificity for vasculature Untargeted exosome Targeted exosome I 125 I 125
Future Directions Acknowledgements Boya Zhang Verify cell-specific delivery Michaela Dodd Layne Bond Deliver functional cargo Xinye Wang Explore other targets by Jae Bucknor Sachith Vidanapathirana swapping affinity ligands Colin Greineder
Normalize of H5C6 exosome fractions 1.0 I125 counts Untargeted exosome: GFP signal Normalized signal 0.8 I 125 0.6 0.4 0.2 0.0 0 20 fractions 40 Normalize of H5C6/YN1 2;2 exosome fractions 1.0 Targeted exosome: I 125 I125 counts Normalized signal 0.8 GFP signal 0.6 0.4 0.2 0.0 0 20 fractions 40
