The incidence of central nervous system (CNS) diseases is increasing year by year. Drug delivery targeting the brain is the best therapy for CNS diseases, but the biggest obstacle to this therapy is the obstruction of the blood-brain barrier (BBB). Promisingly, exosomes are considered a next-generation drug delivery platform due to their good biocompatibility and BBB permeability. However, natural exosomes have the problem of poor tissue targeting. Therefore, it is necessary to engineer exosomes by adding brain-targeting peptides to improve the brain-targeting properties of exosomes. Creative Biolabs can develop a series of targeted modified engineered exosomes for different tissues, and provide high-quality engineered exosome construction and verification services to help researchers develop efficient and safe exosome drugs.

Engineered Exosomes Modified with Brain-Targeting Peptides

Among the brain-targeting peptides, rabies virus glycoprotein (RVG) is widely used and widely recognized. RVG is the only structural protein exposed outside the rabies virus membrane. RVG selectively targets neuronal cells and brain endothelial cells by binding to the nicotinic acetylcholine receptor (nAChR). So far, numerous studies have shown that RVG peptide-modified exosomes (RVG-Exo) can serve as an efficient and safe drug delivery vehicle. RVG-Exo can deliver almost all small and macromolecular drugs, including siRNAs, microRNAs, DNA, proteins, and other nanoparticles. The loading of these drugs is achieved by further applying electroporation to RVG-Exo. Currently, there are mainly two strategies for RVG modification of exosomes.

• Donor cells that secrete exosomes are bioengineered. RVG and lysosome-related membrane glycoprotein 2b (Lamp2b), an exosome membrane-localized protein, are constructed in the same plasmid (Lamp2b-RVG plasmid) for fusion expression. By transiently transfecting Lamp2b-RVG plasmids into donor cells or constructing stably transfected cell lines that continuously express Lamp2b-RVG, a large number of engineered exosomes expressing RVG on the surface can be extracted. The above method is the most mainstream strategy for RVG modification of exosomes.

Fig.1 Schematic diagram of the production and harvest of engineered RVG-EVs for targeted circDYM delivery. (Zhang, 2022)

• The isolated exosomes are physically modified. Phospholipid molecules and RVG are constructed into complexes. These complexes can be inserted into the exosomal phospholipid bilayer through hydrophobicity. Therefore, engineered exosomes with RVG on the surface can be obtained.

Fig.2 Scheme of REXO-C/ANP/S preparation. (Liu, 2020)

At present, RVG-Exo has been explored in the treatment of stroke, severe depression, Parkinson's disease, Alzheimer's disease, and other CNS diseases. In the future, brain-targeted engineered exosomes, including RVG-Exo, have great prospects and value and are expected to be used to develop drugs. Creative Biolabs can provide customers with innovative drug research services using brain-targeted exosomes as drug delivery systems. Please contact us with your needs and ideas to help you move forward with your project.

References

1. Yu, X.; Bai Y.; et al. Extracellular vesicle-mediated delivery of circDYM alleviates CUS-induced depressive-like behaviours. Journal of Extracellular Vesicles. 2022. 11:e12185.
2. Liu, L.; Li, Y.; et al. Targeted exosome coating gene-chem nanocomplex as "nanoscavenger" for clearing α-synuclein and immune activation of Parkinson's disease. Science Advances. 2020. 6(50).

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