Gene transfection by cationic liposome with a cationic cholesterol derivative

阳离子脂质体与阳离子胆固醇衍生物的基因转染

• 批准号: 12557207
• 负责人: NAKANISHI Mamoru
• 金额: $ 5.7万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557207/
• 关键词: Gene transfection; Cationic cholesterol; Cationic liposome; Non-viral vector; Microscopy; Endocytosis; Biosurfactant; Gene therapy; 非ウイルスベクター; 膜融合

We will demonstrate interesting cationic liposomes with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic force microscopy in elucidating the molecular mechanism of gene transfection by cationic liposomes is also showed using examples from our own work. As delineated, both the confocal laser scanning microscopic and the atomic force microscopic results advocate for the involvement of the sequential three steps in gene transfection mediated by the cationic liposomes: endocytotic internalization of the lipoplexes into the target cells, endosome-lysosome fusion whereby the DNA gets released from the liposomes and moves towards the nucleus of the target cells and microtubule organization apparently involved in trafficking the transfected foreign genes to lysosomes. Furthermore, our experiment also shows couple of important strategies in gene transfection namely, use of liposomes made from biosurfactans and harnessing efficient gene transfection by activating the membrane-bound receptor molecules.

我们将展示具有新型阳离子胆固醇衍生物的有趣阳离子脂质体，这是我们组开发的基因转染的新策略以及目前接受的基因转染的分子机制。使用我们自身工作的示例，还显示了共聚焦激光扫描显微镜和原子力显微镜在阐明阳离子脂质体基因转染基因转染的分子机制中。如图所示，共聚焦激光扫描显微镜和原子力显微镜结果倡导了由阳离子脂质体介导的顺序三个步骤参与基因转染的三个步骤：脂质体的内吞脂肪内在化，将脂质体内化为脂质体内，将脂质体内化到靶细胞中，而叶片组融合到靶细胞，内体 - 溶质体融合，在某些情况下，DNA，DNA，脂质体。从脂质体中释放出来，向靶细胞的核和微管组织的核移动，显然参与了将转染的外源基因运输到溶酶体中。此外，我们的实验还显示了基因转染中的几个重要策略，即使用由生物表层制成的脂质体，并通过激活膜结合的受体分子来利用有效的基因转染。

项目成果

Noguchi, S., Hirashima, N., Furuno, T., Nakanishi, M.: "Remarkable induction of apoptsis in cancer cells by a novel cationic liposome complexed with a bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

Noguchi, S.、Hirashima, N.、Furuno, T.、Nakanishi, M.：“与 bcl-2 反义寡核苷酸复合的新型阳离子脂质体显着诱导癌细胞凋亡”J Control Release。

Noguchi, A., Hirashima, N., Furuno, T., Nakanishi, M.: "Activation of receptor tyrosine kineses promotes gene transfection in the neuronal PC12 cells by cationic liposomes"Neurosci. Lett.. (in press).

Noguchi, A.、Hirashima, N.、Furuno, T.、Nakanishi, M.：“受体酪氨酸激酶的激活通过阳离子脂质体促进神经元 PC12 细胞中的基因转染”Neurosci。

Noguchi, S., Hirashima, N., Furuno, T., Nakanishi, M.: "Remarkable induction of apoptsis in cancer cells by a novel cationic liposome complexed with bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

Noguchi, S.、Hirashima, N.、Furuno, T.、Nakanishi, M.：“与 bcl-2 反义寡核苷酸复合的新型阳离子脂质体显着诱导癌细胞凋亡”J Control Release。

Noguchi,S., Hirashima,N., Furuno,T., Nakanishi,M.: "Remarkable induction of apoptosis in cancer cells by a novel cationic liposome conplexed with a bcl-2 antisense oligonucleotide"J Control Release. 7. 313-320 (2003)

Noguchi,S.、Hirashima,N.、Furuno,T.、Nakanishi,M.：“与 bcl-2 反义寡核苷酸复合的新型阳离子脂质体显着诱导癌细胞凋亡”J Control Release。

中西 守 他: "免疫学辞典"東京化学同人. 450 (2002)

Mamoru Nakanishi 等：《免疫学词典》东京化学同人450（2002）。