Bi-target treatment for bladder cancer by non-fusion Adeno-associated virus carrier of tumstatin Tumstatin and suicide gene HSV-TK

Abstract

Since 1990, gene therapy as the 5th new complementary therapy for tumor has become the most prospective method for human to conquer cancer. However, the gene therapy of bladder cancer still has the following inevitable problems that: (1), the core technology of the gene therapy is to select a carrier with high expression, low immunogenicity, no insertion teratogenesis and good biological safety; (2), because the occurrence and the development of the tumor are a process of multi-gene and multi-channel regulation, the anti-tumor effect of the gene therapy for regulating cell differentiation and accelerating an apoptosis process for a single target is limited; and (3), fusion gene therapy may weaken even inactivate the anti-tumor effect of another gene. Therefore, a non-fusion Adeno-associated virus (AVV) carrier of tumstatin Tumstatin and suicide gene HSV-TK for resisting tumor angiogenesis specifically and highly efficiently is constructed by adopting a technical platform of a gene Adeno-associated virus (AVV) carrier with high biological safety and low immunogenicity. Because the AVV has high affinity to bladder cancer cells, the AVV makes infected bladder cancer cells continuously expressed and secrete the tumstatin to inhibit angiogenesis, the non-fusion Adeno-associated virus (AVV) carrier enhances the sensitivity of the tumor to a prodrug and the suicide gene in an ischemia state and treats the bladder cancer by cooperating with double targets to fulfil the aim of treating the tumor and preventing the tumor from relapsing.

Description

technical field The present invention mainly relates to the field of tumor gene therapy, and more specifically refers to constructing a recombinant AAV vector (rAAV-TK-IRES-Tu) for non-fusion dual-target expression of tumorstatin (Tumstatin) and suicide gene (TK) through gene recombination technology , and after virus packaging and purification to obtain high-purity and high-concentration virus particles, the virus particles are used to inhibit the growth of solid tumors and their blood vessels. Background technique Bladder cancer is the most common malignant tumor of the urinary system. Surgery is the main treatment. If no other treatment is given after surgery, the short-term recurrence rate is 60-90%, and the long-term recurrence rate is almost 100%. However, due to local radiotherapy and Systemic chemotherapy has serious side effects and drug resistance, so it is hardly used in clinical practice at present. Intravesical biological immunotherapy is an effective adjuvant ...

AI Technical Summary

Problems solved by technology

However, there are still some unavoidable problems in the gene therapy of bladder cancer: ①The selection of high expression, low immunogenicity, no insertional teratogenicity and good biosafety vector is the core technology of gene therapy; ②The occurrence and development of tumors It is a mult

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