Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes

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Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes
Title:
Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes
Journal Title:
EMBO Molecular Medicine
Keywords:
Publication Date:
06 March 2024
Citation:
Han, G., Zhang, Y., Zhong, L., Wang, B., Qiu, S., Song, J., Lin, C., Zou, F., Wu, J., Yu, H., Liang, C., Wen, K., Seow, Y., & Yin, H. (2024). Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes. EMBO Molecular Medicine, 16(4), 1027–1045. https://doi.org/10.1038/s44321-024-00049-7
Abstract:
Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
There was no specific funding for the research done
Description:
This is the final published version of the article published in EMBO Molecular Medicine, available under a Creative Commons Attribution License (CC BY). The original publication can be accessed at 10.1038/s44321-024-00049-7
ISSN:
1757-4684