HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium
HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium
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HVJ（仙台病毒）-阳离子脂质体：一种新颖且潜在有效的脂质体介导技术，用于将基因转移到气道上皮
DOI：
10.1038/sj.gt.3300463
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发表时间：
1997
期刊：
影响因子：
5.1
通讯作者：
K. Sueishi
中科院分区：
文献类型：
--
作者：
Y. Yonemitsu;Y. Kaneda;A. Muraishi;T. Yoshizumi;K. Sugimachi;K. Sueishi
我们设计了一种将靶向基因转移到气道上皮的新技术。采用多层阳离子脂质体构建，含有N-(α-三甲基乙酰氨基)-双十二烷基-D ox-谷氨酸氯化物、磷脂酰胆碱和胆固醇，并与日本血凝病毒(HVJ)融合，即HVJ阳离子脂质体。将这种新型载体单次气雾递送至大鼠气道，导致异硫氰酸荧光素标记的寡核苷酸或lacZ基因高效且广泛地转导至支气管上皮和肺泡巨噬细胞，但不转导至肺泡上皮。单次施用lacZ基因将基因转移至气道上皮的效率在气管中约为47.6%，在支气管和近端细支气管中为39.0%，在终末细支气管中为2.9%（平均值，n=6）。在气管和肺组织中，用这种新系统传递的荧光素酶基因的表达水平比没有 HVJ 的表达水平高得多。每隔一周两次预处理 HVJ-阳离子脂质体载体导致上皮下层的炎症浸润最小化，并且随后的基因转移效率没有显着降低。我们认为，这种新型 HVJ 阳离子脂质体介导的基因转移系统可能适用于临床基因治疗，以治疗患有囊性纤维化等致命性肺部疾病的受试者。
We designed a novel technique for targeted gene transfer into the airway epithelium. This was constructed using multilamellar cationic liposomes, containing N-(α-trimethylammonioacetyl)-didodecyl-D ox-glutamate chloride, phosphatidylcholine and cholesterol and fused with haemagglutinating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel vector to the airway of rats led to a highly efficient and widespread transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene into the bronchial epithelium and alveolar macrophages, but not into the alveolar epithelium. The efficiency of gene transfer to the airway epithelium with a single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli, respectively (mean value, n= 6). Expression level of the luciferase gene delivered with this novel system was much higher than that without HVJ, in both the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles every other week resulted in minimal inflammatory infiltration in the subepithelial layer with no significant reduction in efficiency of the following gene transfer. We propose that this novel HVJ cationic liposome-mediated gene transfer system may be suitable for clinical gene therapy to treat subjects with lethal lung diseases such as cystic fibrosis.