Kaneda Yasufumi
Osaka University Graduate School of Medicine, Division of Gene Therapy Science, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Expert Opin Drug Deliv. 2008 Feb;5(2):221-33. doi: 10.1517/17425247.5.2.221.
Efficient and minimally invasive vector systems appear to be the most appropriate for both gene therapy and drug delivery. Numerous viral and non-viral vectors have been developed. Each vector has its own advantages and limitations.
New vectors have been required for overcoming the limitations of both viral vectors and non-viral vectors. The idea is to compensate the limitations of one vector system with the advantages of another. This can enable efficient drug delivery and gene expression, while reducing the cytotoxicity of the various vector components.
The Hemagglutinating Virus of Japan (HVJ; Sendai virus) envelope vector was developed using fusion-competent inactivated HVJ particle. Briefly, the viral genome was destroyed by UV-irradiation, and the inactivated viral particles were mixed with plasmid DNA, proteins or siRNA in the presence of mild detergent. After centrifugation, those molecules were incorporated into the viral envelope.
The HVJ-E vector can efficiently deliver therapeutic molecules such as genes, siRNA, decoy oligonucleotides, proteins, and anti-cancer drugs to various tissues in vivo. It is also available for high throughput screening of therapeutic genes. A number of anti-cancer effects of HVJ-E have been identified, specifically activation of both T cell immunity and non-T cell immunity against cancers. Furthermore, a tissue-targeting HVJ-E vector has been constructed using a unique approach for virus engineering and by conjugation with biocompatible polymers. Therefore, the HVJ-E vector is expected to enable effective cancer therapy through the delivery of molecular therapy and through its immunotherapeutic effects.
高效且微创的载体系统似乎最适合基因治疗和药物递送。已经开发了许多病毒和非病毒载体。每种载体都有其自身的优点和局限性。
需要新的载体来克服病毒载体和非病毒载体的局限性。其理念是用另一种载体的优点来弥补一种载体系统的局限性。这可以实现高效的药物递送和基因表达,同时降低各种载体成分的细胞毒性。
日本血凝病毒(HVJ;仙台病毒)包膜载体是利用具有融合能力的灭活HVJ颗粒开发的。简而言之,病毒基因组通过紫外线照射被破坏,并且在温和去污剂存在的情况下,将灭活的病毒颗粒与质粒DNA、蛋白质或小干扰RNA混合。离心后,这些分子被整合到病毒包膜中。
HVJ-E载体可以在体内将治疗性分子如基因、小干扰RNA、诱饵寡核苷酸、蛋白质和抗癌药物有效地递送至各种组织。它也可用于治疗性基因的高通量筛选。已经确定了HVJ-E的许多抗癌作用,特别是激活针对癌症的T细胞免疫和非T细胞免疫。此外,已经使用独特的病毒工程方法并通过与生物相容性聚合物缀合构建了组织靶向性HVJ-E载体。因此,预计HVJ-E载体能够通过分子治疗的递送及其免疫治疗作用实现有效的癌症治疗。