| RRC ID |
12036
|
| Author |
Maeda M, Namikawa K, Kobayashi I, Ohba N, Takahara Y, Kadono C, Tanaka A, Kiyama H.
|
| Title |
Targeted gene therapy toward astrocytoma using a Cre/loxP-based adenovirus system.
|
| Journal |
Brain Res
|
| Abstract |
The aim of this study was to establish a novel adenovirus-based gene therapy system targeting astrocytoma. For this purpose, the Cre recombinase (Cre)/loxP system together with the astrocytoma-specific promoter for GFAP were used. We constructed an adenovirus (Ad) vector that expressed Cre under the control of the GFAP promoter (AxGFAPNCre), as well as another Ad vector containing a switching unit. The latter vector contained a stuffer sequence encoding GFP (AxCALGLTK) with a functional polyadenylation signal between two loxP sites, followed by the herpes simplex virus thymidine kinase (HSV-TK) gene under the control of the CAG promoter. In this system, gene expression of either the stuffer sequence (GFP) or the downstream gene (HSV-TK) was switched on by co-expression of Cre recombinase. Western blot analysis demonstrated specific expression of high levels of TK protein in C6 glioma cells after co-infection of AxGFAPNCre and AxCALGLTK. In vivo, AxGFAPNCre/AxCALGLTK injection into C6 gliomas in the subcutaneous tissue of nude mice followed by intraperitoneal ganciclovir (GCV) treatment significantly suppressed tumor growth compared with control mice. Co-infection of AxGFAPNCre and AxCALNLLacZ resulted in LacZ expression in C6 glioma cells and some reactive astrocytes, whereas GFP was expressed in other cell types surrounding the injected site. Furthermore, a combination of AxGFAPNCre/AxCALGLTK and intraperitoneal GCV injection significantly regressed intracranial C6 gliomas in the rat striatum and prolonged the survival time compared with control rats. The present results indicate that this cell-type-specific gene therapy using a Cre/loxP adenovirus system is both operational and effective, at least against astrocytoma.
|
| Volume |
1081(1)
|
| Pages |
34-43
|
| Published |
2006-4-7
|
| DOI |
10.1016/j.brainres.2006.01.105
|
| PII |
S0006-8993(06)00252-6
|
| PMID |
16529724
|
| MeSH |
Adenoviridae / genetics
Animals
Astrocytoma / pathology
Astrocytoma / therapy*
Blotting, Western / methods
Brain Neoplasms / pathology
Brain Neoplasms / therapy
Brain Neoplasms / virology
Dose-Response Relationship, Drug
Extracellular Matrix Proteins / biosynthesis
Extracellular Matrix Proteins / genetics
Extracellular Matrix Proteins / therapeutic use*
Gene Transfer Techniques
Genetic Therapy* / methods
Humans
Immunohistochemistry / methods
Integrases / biosynthesis
Integrases / genetics
Integrases / therapeutic use*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation / methods
Protein-Lysine 6-Oxidase / biosynthesis
Protein-Lysine 6-Oxidase / genetics
Protein-Lysine 6-Oxidase / therapeutic use*
Rats
Rats, Wistar
Time Factors
Tumor Cells, Cultured
Viral Proteins / biosynthesis
Viral Proteins / genetics
Viral Proteins / therapeutic use*
|
| IF |
2.733
|
| Times Cited |
15
|
|
WOS Category
|
NEUROSCIENCES
|
| Resource |
| DNA material |
pCALwL (RDB1679) |
