| Autor: |
Hirofumi Hamada, Kiminori Nakamura, Kazuhiro Takahashi, Kazunori Kato, Katsunori Sasaki, Masayoshi Kobune, Hironari Dehari, Katsuya Ikeda, Hiroaki Uchida, Yoshinori Ito, Jianhua Huang |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
The Journal of Gene Medicine. 5:900-908 |
| ISSN: |
1099-498X |
| DOI: |
10.1002/jgm.429 |
| Popis: |
Background Although naked plasmid injection is the safest and most convenient method for gene delivery, a major limitation of this approach is currently poor transgene expression. The CA promoter (chicken β-actin promoter with cytomegalovirus, CMV, enhancer) is one of the strongest transcriptional control modules found; however, it is uncertain whether a CA promoter-based vector is efficient enough for naked gene therapy in a cardiovascular context. Methods The β-galactosidase (LacZ) expression provided by CA promoter plasmid (pCAZ2) injection into the skeletal muscle or the heart of Lewis rats was compared with CMV promoter plasmid or adenoviral vector (AxCAZ3). The effect of Simian virus 40 of the replication origin (SV40ori) deletion from pCAZ2 on transgene expression was also evaluated. Results pCAZ2 showed the highest LacZ expression in both skeletal muscle and heart in comparison with the CMV promoter-based vector 5 days after naked plasmid injection. LacZ expression in the heart obtained using 20 µg of pCAZ2 was almost equivalent to that shown with AxCAZ3 at 6.0 × 109 optical particle units. The time course of transgene expression driven by CMV and CA promoters in the heart were similar, with the CA promoter providing significantly higher gene expression than the CMV promoter across all time points examined. SV40ori deletion from pCAZ2 did not affect transgene expression in either skeletal muscle or heart. Conclusions Transgene expression mediated by naked CA promoter-based plasmid injection was shown to be quite efficient in the heart. We propose that the CA promoter vector is suitable for myocardial gene therapy. Copyright © 2003 John Wiley & Sons, Ltd. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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