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转铁蛋白受体靶向性HVJ-E载体的研发

Development of a transferrin receptor-targeting HVJ-E vector.

作者信息

Shimbo Takashi, Kawachi Masako, Saga Kotaro, Fujita Hiroshi, Yamazaki Takehiko, Tamai Katsuto, Kaneda Yasufumi

机构信息

Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

出版信息

Biochem Biophys Res Commun. 2007 Dec 21;364(3):423-8. doi: 10.1016/j.bbrc.2007.09.135. Epub 2007 Oct 12.

Abstract

The development of more effective cancer treatments is anticipated. Tumor-targeted drug delivery is an important strategy in cancer therapy. We have developed an HVJ (hemagglutinating virus of Japan; Sendai virus) envelope (HVJ-E) vector using inactivated Sendai virus. The HVJ-E vector has been observed to target a number of cell lines since its hemagglutinin-neuraminidase (HN) protein recognizes the sialic acids of host cells. Thus, to reduce non-specific binding of the HVJ-E vector, we eliminated HN protein using HN-specific short interfering RNA (siRNA). Then, to further increase its tumor-targeting ability, we constructed HN-depleted HVJ containing the F-transferrin chimeric protein. The modified vectors containing Q-dots demonstrated 32-fold greater tumor-targeting efficiency than wild-type HVJ-E.

摘要

预计会开发出更有效的癌症治疗方法。肿瘤靶向给药是癌症治疗中的一项重要策略。我们利用灭活的仙台病毒开发了一种HVJ(日本血凝病毒;仙台病毒)包膜(HVJ-E)载体。由于其血凝素神经氨酸酶(HN)蛋白能识别宿主细胞的唾液酸,因此观察到HVJ-E载体可靶向多种细胞系。因此,为了减少HVJ-E载体的非特异性结合,我们使用HN特异性小干扰RNA(siRNA)消除了HN蛋白。然后,为了进一步提高其肿瘤靶向能力,我们构建了含有F-转铁蛋白嵌合蛋白的HN缺失型HVJ。含有量子点的修饰载体显示出比野生型HVJ-E高32倍的肿瘤靶向效率。

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