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Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.
Han, Gang; Zhang, Yao; Zhong, Li; Wang, Biaobiao; Qiu, Shuai; Song, Jun; Lin, Caorui; Zou, Fangdi; Wu, Jingqiao; Yu, Huanan; Liang, Chao; Wen, Ke; Seow, Yiqi; Yin, HaiFang.
Afiliación
  • Han G; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Zhang Y; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Zhong L; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Wang B; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Qiu S; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Song J; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Lin C; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Zou F; Public Laboratory & Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center & Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China.
  • Wu J; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Yu H; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
  • Liang C; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, 518055, Shenzhen, China.
  • Wen K; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
  • Seow Y; Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis St, Genome, Singapore, 138672, Republic of Singapore.
  • Yin H; State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, T
EMBO Mol Med ; 16(4): 1027-1045, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38448545
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Distrofia Muscular de Duchenne / Exosomas Límite: Animals Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Distrofia Muscular de Duchenne / Exosomas Límite: Animals Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Alemania