Yasufumi Kaneda1. 1. Osaka University Graduate School of Medicine, Division of Gene Therapy Science, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. kaneday@gts.med.osaka-u.ac.jp
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. CONCLUSION: 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.