Atelocollagen-mediated systemic DDS for nucleic acid medicines
Atelocollagen-mediated systemic DDS for nucleic acid medicines
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DOI：
10.1196/annals.1348.010
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
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作者：
Hanai, Koji;Takeshita, Fumitaka;Ochiya, Takahiro
我们研究的目标是为寡核苷酸治疗中的药物输送提供一个实用的平台。我们在此报告了去端肽胶原介导的寡核苷酸递送系统应用于动物疾病模型中的系统性 siRNA 和反义寡核苷酸治疗的功效。去端肽胶原和寡核苷酸形成纳米颗粒复合物，对核酸酶高度稳定。该复合物允许通过静脉注射将寡核苷酸有效地递送到多个器官和组织中。在肿瘤转移模型中，该复合物成功地将 siRNA 递送至骨组织中的转移肿瘤并抑制其生长。我们还证明，在接触性超敏反应模型中，反义寡脱氧核苷酸复合物的单次静脉注射治疗可抑制耳部皮炎。这些结果表明去端肽胶原介导的药物递送系统在实用治疗技术方面具有巨大潜力。
The goal of our research is to provide a practical platform for drug delivery in oligonucleotide therapy. We report here the efficacy of an atelocollagen-mediated oligonucleotide delivery system applied to systemic siRNA and antisense oligonucleotide treatments in animal disease models. Atelocollagen and oligonucleotides formed a complex of nanosized particles, which was highly stable against nucleases. The complex allowed oligonucleotides to be delivered efficiently into several organs and tissues via intravenous administration. In a tumor metastasis model, the complex successfully delivered siRNA to metastasized tumors in bone tissue and inhibited their growth. We also demonstrated that a single intravenous treatment of the antisense oligodeoxynucleotide complex suppressed ear dermatitis in a contact hypersensitivity model. These results indicate the strong potential of the atelocollagen-mediated drug delivery system for practical therapeutic technology.