Kaneda Yasufumi
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Curr Drug Targets. 2003 Nov;4(8):599-602. doi: 10.2174/1389450033490740.
Efficient and minimally invasive drug delivery systems have been developed to treat intractable human diseases. One approach has been the development of chimeric vector systems combining at least two different vector systems. Based on this concept, chimeric drug delivery systems that combine viral and non-viral features have been developed. Fusigenic non-viral particles have been constructed by conferring viral fusion proteins onto non-viral vectors. HVJ (hemagglutinating virus of Japan; Sendai virus)-liposomes were constructed by the combination of DNA-loaded liposomes with a fusigenic envelope derived from HVJ (hemagglutinating virus of Japan, Sendai virus). Reconstituted HVJ-liposomes were also developed by the insertion of isolated fusion proteins of HVJ into DNA-loaded liposomes. Recently, the technology has been developed to incorporate macromolecules directly into inactivated HVJ particles without liposomes. The resulting HVJ envelope vector introduced plasmid DNA, efficiently and rapidly into both cultured cells in vitro and organs in vivo. Furthermore, proteins, synthetic oligonucleotides and drugs have also been effectively introduced into cells using the HVJ envelope vector. The HVJ envelope vector will be a promising tool for both ex vivo and in vivo gene therapy experiments.
高效且微创的药物递送系统已被开发用于治疗难治性人类疾病。一种方法是开发至少结合两种不同载体系统的嵌合载体系统。基于这一概念，已开发出结合病毒和非病毒特征的嵌合药物递送系统。通过将病毒融合蛋白赋予非病毒载体，构建了具有融合能力的非病毒颗粒。通过将负载DNA的脂质体与源自日本血凝病毒（仙台病毒）的融合包膜相结合，构建了HVJ（日本血凝病毒；仙台病毒）-脂质体。通过将分离的HVJ融合蛋白插入负载DNA的脂质体中，还开发了重组HVJ-脂质体。最近，已开发出一种技术，可将大分子直接掺入无脂质体的灭活HVJ颗粒中。所得的HVJ包膜载体可将质粒DNA高效、快速地导入体外培养细胞和体内器官。此外，使用HVJ包膜载体也可有效地将蛋白质、合成寡核苷酸和药物导入细胞。HVJ包膜载体将成为用于体外和体内基因治疗实验的有前途的工具。
