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Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.

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 (EXO_EAA-PMO). EXO_EAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXO_EAA-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.

SUBMITTER: Han G

PROVIDER: S-EPMC11018858 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.

Han Gang G Zhang Yao Y Zhong Li L Wang Biaobiao B Qiu Shuai S Song Jun J Lin Caorui C Zou Fangdi F Wu Jingqiao J Yu Huanan H Liang Chao C Wen Ke K Seow Yiqi Y Yin HaiFang H

EMBO molecular medicine 20240306 4

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 exoso ...[more]

PMID: 38448545

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Dataset Information

Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.

Publications

Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.

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