聚乙烯亞胺接枝醣的共聚物做為基因載體POLYSACCHARIDE-GRAFTED POLYETHYLENIMINE AS A GENE CARRIER

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

13/299,826

專利證號

US 8,716,399 B2

專利獲證名稱

聚乙烯亞胺接枝醣的共聚物做為基因載體POLYSACCHARIDE-GRAFTED POLYETHYLENIMINE AS A GENE CARRIER

專利所屬機關 (申請機關)

高雄醫學大學

獲證日期

2014/05/06

技術說明

聚乙烯亞胺是一個極具有潛力的基因載體，本身擁有高轉染能力以及緩衝能力，在細胞內脂體(Endosomes)能持續地被質子化，使得大量的氯離子湧入，提高滲透壓，進而造成細胞內脂體的漲破，將所攜帶的基因藥物(DNA 或siRNA)釋放到細胞質中，發揮療效功能。雖然聚乙烯亞胺擁有這些優點，但是高毒性仍然是做為臨床應用需要克服的問題。聚乙烯亞胺毒性來自於它穿透細胞膜的能力，因此本實驗中我們引進帶負電荷的天然多醣體-硫酸化軟骨素，調控正負電荷比來形成奈米結構，藉由不同於聚乙烯亞胺進入細胞的內噬機制，來降低聚乙烯亞胺的毒性，並增加聚乙烯亞胺對基因的轉染能力。 Polyethylenimine is a potential gene delivery vector. The high transfection efficiency of PEI has been postulated to relate to its buffering capacity, which leads to the accumulation of protons brought in by endosomal ATPase and an influx of chloride anions, triggering endosome swelling and disruption, followed by the release of gene drugs into cytoplasm. Although the polymer itself is used as a delivery vehicle for a long while, toxicity is always an issue for clinical applications. Cytotoxicity of PEI is due to its ability to permeabilize cell membranes. In this study, we'll introduce an anionic natural polysaccharide- chondroitin sulfate to PEI and adjust intramolecular electrostatic interactions of CS-modified PEI to form a nanometer-sized conformation, which may use a different mechanism to enter cells. Thus, the cytotoxicity issue of PEI can be minimized and the transfection efficiency can be also enhanced.

備註

本部(發文號1100044017)同意貴校110年1月28日高醫產學字第1101100305號函申請終止維護專利。(高醫)

連絡單位 (專責單位/部門名稱)

智財保護與科技管理組

連絡電話

07-3138030

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