[Development of gene-viral vector and its anti-tumor effect, a primary study].
OBJECTIVE
To develop a new kind of vector system, named as gene-viral vector, which combines the advantages of the gene therapy and virus therapy.


METHODS
An anti-tumor gene was inserted into the genome of the replicative virus specific for the tumor cells by virus recombination technology. The killing effect, report gene expression of the green fluorescence protein, expression of the anti-tumor gene of mouse IL12, and the replication of the virus were observed respectively by cell pathology, fluorescence microscopy, ELISA and electron microscopy.


RESULTS
A new kind of gene-viral vector system, in which the E1b-55 000 gene is deleted but the E1a gene of adenovirus is preserved, was constructed. The vector system possessed the same characteristics as the replicative virus ONYX-015, replication and proliferation in the tumor cells but not in the normal cells, thus specifically killing the tumor cells. Besides, it carried many kinds of anti-tumor genes. When carrying the report gene of the green fluorescence protein it made the expression of this gene in tumor cells far more effectively than the adenovirus vector employed in the traditional gene therapy did. However in the normal cells the expression of green fluorescence protein caused by this vector system was as little as or even less than that by the traditional adenovirus system. The similar result was also observed in the experiments of this vector system carrying the anti-tumor gene, gene of mouse IL12. The replication and proliferation of the virus carrying the gene of mouse IL12 in the tumor cells were confirmed by electron microscopy.


CONCLUSIONS
Gene-viral vector is a new kind of vector in which the anti-tumor gene is inserted into the genome of the replicative virus specific for the tumor cells. It increases the expression of the anti-tumor gene by hundreds even tens of thousand times. It posseses all the advantages of gene therapy and virus therapy, thus further enhancing the curative effect and it overcomes such disadvantages as low transfer rate, low expression, lack of target tropism and low anti-tumor activity. It will become one of the most promising means in tumor treatment.
Qian
Qijun
Q
Viral & Gene Therapy Center, Eastern Hepatobilliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Che
Xiaoyan
X
Cen
Xintang
X
Cui
Zhenfu
Z
Xue
Huibin
H
Zhu
Bin
B
Xu
Jianguo
J
Billy
Wu
Mengchao
M
D000256:Adenoviridae; D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008099:Liver / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D010179:Pancreas / Q000166:cytology; D011995:Recombination, Genetic
D000970:Antineoplastic Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D018664:Interleukin-12