Comparison of gene expression efficiency and innate immune response induced by Ad vector and lipoplex
Vectors for gene expression are the essential tools for both gene therapy and basic research. There are two groups of gene therapy vectors, viral and non-viral vectors. At present, toxicity triggered by vectors is one of the major concerns for clinical trials. In general, non-viral vectors, such as...
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| Published in | Journal of controlled release Vol. 117; no. 3; pp. 430 - 437 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Amsterdam
Elsevier B.V
26.02.2007
Elsevier |
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| Abstract | Vectors for gene expression are the essential tools for both gene therapy and basic research. There are two groups of gene therapy vectors, viral and non-viral vectors. At present, toxicity triggered by vectors is one of the major concerns for clinical trials. In general, non-viral vectors, such as plasmid DNA–cationic liposome complex (lipoplex), are thought to be safer than viral vectors, such as adenovirus (Ad) vector, although lipoplex is less efficient in term of gene expression than the Ad vector. However, there has been no study directly comparing the gene expression efficiency and safety of viral and non-viral vectors. Here, we present evidence that the Ad vector shows much more efficient gene expression and is safer than lipoplex, at least with respect to the innate immune response. After being systemically administered to mice, the Ad vector showed a transduction efficiency that was 2 to 5 log orders higher than that of lipoplex, depending on the organ. On the other hand, surprisingly, the administration of lipoplex produced a greater amount of inflammatory cytokines such as interleukin-6, interleukin-12, and tumor necrosis factor-α than did the administration of the Ad vector, whereas a comparable level of hepatotoxicity was induced by these vectors. The production of inflammatory cytokines induced by the injection of lipoplex was reduced when the CpG motifs were removed completely from plasmid DNA. Thus, care should be taken to ensure the innate immune response induced by gene therapy vectors, especially lipoplex. |
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| AbstractList | Vectors for gene expression are the essential tools for both gene therapy and basic research. There are two groups of gene therapy vectors, viral and non-viral vectors. At present, toxicity triggered by vectors is one of the major concerns for clinical trials. In general, non-viral vectors, such as plasmid DNA-cationic liposome complex (lipoplex), are thought to be safer than viral vectors, such as adenovirus (Ad) vector, although lipoplex is less efficient in term of gene expression than the Ad vector. However, there has been no study directly comparing the gene expression efficiency and safety of viral and non-viral vectors. Here, we present evidence that the Ad vector shows much more efficient gene expression and is safer than lipoplex, at least with respect to the innate immune response. After being systemically administered to mice, the Ad vector showed a transduction efficiency that was 2 to 5 log orders higher than that of lipoplex, depending on the organ. On the other hand, surprisingly, the administration of lipoplex produced a greater amount of inflammatory cytokines such as interleukin-6, interleukin-12, and tumor necrosis factor-alpha than did the administration of the Ad vector, whereas a comparable level of hepatotoxicity was induced by these vectors. The production of inflammatory cytokines induced by the injection of lipoplex was reduced when the CpG motifs were removed completely from plasmid DNA. Thus, care should be taken to ensure the innate immune response induced by gene therapy vectors, especially lipoplex. Vectors for gene expression are the essential tools for both gene therapy and basic research. There are two groups of gene therapy vectors, viral and non-viral vectors. At present, toxicity triggered by vectors is one of the major concerns for clinical trials. In general, non-viral vectors, such as plasmid DNA–cationic liposome complex (lipoplex), are thought to be safer than viral vectors, such as adenovirus (Ad) vector, although lipoplex is less efficient in term of gene expression than the Ad vector. However, there has been no study directly comparing the gene expression efficiency and safety of viral and non-viral vectors. Here, we present evidence that the Ad vector shows much more efficient gene expression and is safer than lipoplex, at least with respect to the innate immune response. After being systemically administered to mice, the Ad vector showed a transduction efficiency that was 2 to 5 log orders higher than that of lipoplex, depending on the organ. On the other hand, surprisingly, the administration of lipoplex produced a greater amount of inflammatory cytokines such as interleukin-6, interleukin-12, and tumor necrosis factor-α than did the administration of the Ad vector, whereas a comparable level of hepatotoxicity was induced by these vectors. The production of inflammatory cytokines induced by the injection of lipoplex was reduced when the CpG motifs were removed completely from plasmid DNA. Thus, care should be taken to ensure the innate immune response induced by gene therapy vectors, especially lipoplex. |
| Author | Mizuguchi, Hiroyuki Sakurai, Haruna Kawabata, Kenji Kurachi, Shinnosuke Huang, Haiying Nakagawa, Shinsaku Sakurai, Fuminori Koizumi, Naoya Tashiro, Katsuhisa Sasaki, Tomomi |
| Author_xml | – sequence: 1 givenname: Haruna surname: Sakurai fullname: Sakurai, Haruna organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 2 givenname: Fuminori surname: Sakurai fullname: Sakurai, Fuminori organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 3 givenname: Kenji surname: Kawabata fullname: Kawabata, Kenji organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 4 givenname: Tomomi surname: Sasaki fullname: Sasaki, Tomomi organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 5 givenname: Naoya surname: Koizumi fullname: Koizumi, Naoya organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 6 givenname: Haiying surname: Huang fullname: Huang, Haiying organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 7 givenname: Katsuhisa surname: Tashiro fullname: Tashiro, Katsuhisa organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 8 givenname: Shinnosuke surname: Kurachi fullname: Kurachi, Shinnosuke organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan – sequence: 9 givenname: Shinsaku surname: Nakagawa fullname: Nakagawa, Shinsaku organization: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan – sequence: 10 givenname: Hiroyuki surname: Mizuguchi fullname: Mizuguchi, Hiroyuki email: mizuguch@nibio.go.jp organization: Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan |
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| Keywords | In vivo gene expression Innate immunity Lipoplex Gene therapy Adenovirus vector Adenoviridae Immune response Pharmaceutical technology Gene expression Immunity Virus In vivo Efficiency Vector Comparative study |
| Language | English |
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| SubjectTerms | Adenoviridae - genetics Adenovirus Adenovirus vector Animals Biological and medical sciences Chemical and Drug Induced Liver Injury - pathology Cytokines - biosynthesis Drug Carriers Excipients Fatty Acids, Monounsaturated Female Gene Expression - physiology Gene therapy General pharmacology Genetic Vectors - administration & dosage Genetic Vectors - adverse effects Immunity, Innate - physiology In vivo gene expression Innate immunity Interleukin-12 - biosynthesis Interleukin-6 - biosynthesis Lipoplex Liposomes Liver - metabolism Liver - ultrastructure Medical sciences Mice Mice, Inbred C57BL Paraffin Embedding Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Plasmids - chemistry Plasmids - genetics Quaternary Ammonium Compounds Transduction, Genetic Tumor Necrosis Factor-alpha - biosynthesis |
| Title | Comparison of gene expression efficiency and innate immune response induced by Ad vector and lipoplex |
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