東北大学 · 生化学・遺伝学・分子生物学
阿部健孝教授の研究室では、がん治療を目的とした新規がん血管遮断型遺伝子医療の開発を主眼としています。特に、腎細胞癌のような化学療法に耐性を示す難治性のがんに対して、pDNAを効率的に腫瘍細胞に届けるためのリポソーム型ナノ粒子(LNP)の開発を進めています。そのカギとなるのが、酸性環境(内嚮体/リソソーム)と還元環境(サイトソール)の両方を感知する「ssPalm」と呼ばれる新規脂質様材料です。この材料により、遺伝子の細胞内解放と核内送達が効率化され、がん細胞の新生血管を標的にした効果的な遺伝子治療が実現可能です。
Figures are computed from collected data and may differ slightly.
SS-cleavable proton-activated lipid-like material (ssPalm) functions as a key element in a lipid nanoparticle in which pDNA is encapsulated. The ssPalm contains dual sensing motifs that can respond to the intracellular environment; a proton-sponge unit (tertiary amines) that functions in response to an acidic environment (endosome/lysosome), and disulfide bonding that can be cleaved in a reducing environment (cytosol).
In the present study, the nuclear delivery of a green fluorescence protein (GFP)-encoding pDNA condensed by protamine was investigated in terms of trans-gene expression after cytoplasmic (E(cyt)) and nuclear (E(nuc)) microinjection. To compare the nuclear transfer process, a novel parameter; the nuclear transfer (NT) score was introduced. The E(cyt) value for protamine/pDNA particles increased in a charge ratio-dependent manner. The calculated NT score showed that this increase results from an e
A renal cell carcinoma (RCC) is one of the refractory tumors, since it readily acquires resistance against chemotherapy. Thus, alternative therapeutic approaches such as obstructing the neovasculature are needed. We previously reported on the development of a plasmid DNA (pDNA)-encapsulating liposomal nanoparticle (LNP) as a hepatic gene delivery system that is applicable to systemic administration. The key molecular component is a SS-cleavable and pH-activated lipid-like material (ssPalm) that
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