Exosomes are natural carriers of proteins, lipids, and nucleic acids and play vital roles in cell-to-cell communication. This property of exosomes has been utilized for genetically engineered the molecular composition of exosomes with exogenous proteins and ligands. When displayed on the surface of exosomes, these molecules show increased solubility/functionality and can be used for a wide range of applications, including drug discovery, ligand screening, and targeted drug delivery. Creative Biolabs utilizes this technology, termed exosome display, for different research purposes and to promote clinical applications.
Exosomes comprise various membrane proteins, such as endosome-associated proteins (Alix, Tsg101, and Rab proteins), tetraspanins (CD63, CD81, CD82, CD53, and CD37), and lipid raft-associated proteins (glycosylphosphatidylinositol and flotillin). The protein contents of exosomes can be manipulated and tailored to endow the exosomes with new desirable properties. Specifically, molecules can be genetically fused to the exosomal transmembrane proteins, expressed on the surface, and endowed with various physiological properties, such as to confer targeting capability, exhibit increased expression levels, offer enhanced solubility and extended half-life, and trigger antigen immunogenicity. These advantageous properties of recombinant exosomes can be applied to different applications, such as antibody generation, targeted drug delivery for gene therapy, as well as ligand screening of G protein-coupled receptors (GPCRs). Molecules that can be displayed on the surface of exosomes include GPCRs and ligand fragments/homing peptides.
Fig.1 Membrane proteins on exosome surface. (Yang, 2018)
Exosome display technology can be used to generate antibodies against different targets, including GPCRs. These targets can be soluble proteins, extracellular domains of the receptors, and integral membrane proteins. On one hand, the former two can be addressed to the surface of exosomes by fusing to targeting molecules, such as the tetraspanins. Antigens such as tumor biomarkers (e.g., cytokines) can be displayed for induction of antibody response. On the other hand, GPCRs can be displayed for drug discovery. Besides, this technology opens up new possibilities for designing novel therapies and generating novel diagnostic tools.
Ligand fragments/homing peptides addressed on the exosomal surface confer exosome targeting capability, which has been used for the targeted delivery of chemotherapy drugs and RNA therapeutics (e.g., siRNAs, miRNA). The targeting moieties can be chosen based on the interested tissues, and the exosomal membrane protein selected as fusion partners also vary.
Because Exosome Display provides a convenient platform to present membrane proteins in a native conformation and environment, recombinant exosomes bearing putative drug targets could also be used to screen cognate ligands or small molecules. For instance, recombinant exosomes expressing GPCR may potentially be used in protein array screen to identify new drugs.
Creative Biolabs is a word-leading company that provides a full range of exosome-related servicesn ranging from exosome isolation to engineering. Exosome display is one of the most distinctive services, which is optimal for antibody generation and isolation, targeted delivery, and protein array screen. If you are interested in our services, contact us to discuss your requirements.