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首页> 外国专利> Long-term siRNA Nanoparticles for genes drug delivery with siRNA for the long -term treatment of retinal disorders and method for preparing the same

Long-term siRNA Nanoparticles for genes drug delivery with siRNA for the long -term treatment of retinal disorders and method for preparing the same

机译：用于长期治疗视网膜疾病的用siRNA进行基因药物递送的长期siRNA纳米颗粒及其制备方法

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摘要

The present invention relates to particles to effectively transfer a lot of siRNA into a retina by coating the outer sides of the high molecular weight of siRNA core particles which are self-assembled and condensed, sequentially with cationic polymer and a hyaluronic acid; and a manufacturing method thereof. The core of the present invention includes 1 x 10^6 or more of small interfering RNA (siRNA) or antisense nucleic acids and thus a lot of the siRNA can be transferred compared to the conventional technique. The present invention can prevent aggregation with vitreous body meshwork structural materials having a (-) charge and reach to an inner limiting membrane of the retina by coating the outer side (shell) with the hyaluronic acid having a (-) charge. Moreover, the hyaluronic acid can pass a sub-retinal space in the structure of the retina based on a transcytosis mechanism by being combined with CD44 receptor of a Muller cell. A part of the hyaluronic acid suppresses mRNA translation of a target gene inside the Muller cell and many parts are inserted into the cell by combining with a CD44 receptor in a retinal pigment epithelial (RPE) cell membrane and suppress the mRNA translation of the target gene inside the RPE.
机译：本发明涉及通过用阳离子聚合物和透明质酸顺序地涂覆自组装并缩合的高分子量siRNA核心颗粒的外侧来有效地将许多siRNA转移到视网膜中的颗粒。及其制造方法。本发明的核心包括1×10 6或更多个小干扰RNA（siRNA）或反义核酸，因此与常规技术相比，可以转移许多siRNA。本发明可以通过用具有（-）电荷的透明质酸涂覆外侧（壳）来防止具有（-）电荷的玻璃体网状结构材料的聚集并且到达视网膜的内部限制膜。此外，透明质酸可通过与Muller细胞的CD44受体结合而基于转胞吞作用机制通过视网膜结构中的视网膜下空间。透明质酸的一部分抑制Muller细胞内部目标基因的mRNA翻译，而许多部分则通过与视网膜色素上皮（RPE）细胞膜中的CD44受体结合而插入到细胞中，并抑制目标基因的mRNA翻译在RPE中。

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