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Method for regulating replication of nonreplication adenovirus

A non-replicating virus, non-replicating technology, applied in the field of biomedicine, can solve problems such as therapeutic gene restriction, and achieve the effect of simplifying construction

Inactive Publication Date: 2006-05-31
李川源 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this way, only smaller genes can be inserted into the virus, which greatly limits the choice of therapeutic genes

Method used

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  • Method for regulating replication of nonreplication adenovirus

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Effect test

Embodiment 1

[0015] 1. Construction of highly selective replication adenovirus in tumor cells

[0016] The first condition for constructing tumor-specific replication-competent viruses is to express the genes necessary for adenoviral replication only in tumor cells. The present invention utilizes the promoters of tumor-specifically expressed genes to control the expression of early genes necessary for adenovirus replication. The early genes include: E1a, E1b, E2a, E2b and E4. The tumor-specific promoters include: tumor cell or microenvironment-specific promoters, hypoxia-inducible gene promoters, E2F1 gene promoters, Midikin gene promoters, telomerase (TERT) gene promoters , heat shock protein gene promoter, tumor tissue-specific promoter, prostate tissue-specific antigen gene promoter, MUC1 gene promoter, lung cell surface protein gene promoter, α-fetoprotein, thyroglobulin (Thyroglobulin) gene promoter, Tyrosinase gene promoter, Myelin Basic protein gene promoter, lactalbumin (lactalbu...

Embodiment 2

[0037] Construct non-replicating adenovirus, and detect the ability of replicating virus to regulate and drive the replication of non-replicating virus.

[0038] The present invention has constructed and amplified the following non-replicating viruses:

[0039] AdCMV-GFP, which carries green fluorescent protein (GFP) from marine organisms.

[0040] AdCMV-TNFα, which carries the gene encoding tumor necrosis factor TNFα.

[0041] The construction and amplification methods of the above-mentioned viruses are the same as the above-mentioned replication-type viruses.

[0042] The titer of the amplified non-replicating virus reaches 3-5×10 7 pfu / ml.

[0043] The non-replicating virus also carries various tumor therapeutic genes as follows:

[0044] Apoptosis-inducing genes (such as TNF-α, TRAIL, etc.);

[0045] Anti-angiogenesis genes (such as endostatin, angiostatin, ex-flk1, ex-Tie2, ex-flt1, PL4, thrombospondin-1, etc.);

[0046] Suicide genes (such as Hsv-tk, cytosine deami...

Embodiment 3

[0052] Non-replicating viruses efficiently replicate in tumor cells under the control and drive of replicating viruses.

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Abstract

The invention belongs to the field of biomedicine and relates to a combined adenovirus tumor gene therapy method, in particular to a method for regulating the replication of non-replicating adenovirus by replicating adenovirus. The invention combines the adenovirus capable of highly selectively replicating in tumor cells with the non-replicating adenovirus carrying various therapeutic genes to perform tumor gene therapy. The invention can effectively utilize the advantages of the two viruses, overcome their respective weaknesses, and make the tumor gene therapy based on the adenovirus more flexible and more targeted.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a combined adenovirus tumor gene therapy method, in particular to a method for regulating the replication of non-replicating adenovirus by replicating adenovirus. Background technique [0002] In recent years, surgical treatment, chemotherapy and radiotherapy of tumors have been significantly improved, and the survival period of cancer patients has gradually increased. However, these improvements are still only applicable to early, localized lesions, and the "therapeutic window" between normal and tumor cells is still very narrow and difficult to widen. The above method also causes severe damage to the patient's normal cells, especially the hematopoietic and immune systems, while killing tumor cells. Therefore, most tumors cannot be cured, and tumors are still one of the most important diseases that endanger human health and life. [0003] In recent years, the progress and achievements ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00C12N7/01A61P35/00
Inventor 李川源黄倩
Owner 李川源
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