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Cancer-targeting recombinant oncolytic gene-adenovirus and construction method and application thereof

An adenovirus and gene technology, applied in the field of oncolytic adenovirus, can solve the problems of less reports on the role of pancreatic cancer, hidden onset, and loss of effective surgical treatment for advanced patients, and achieve good anti-pancreatic cancer effect and low toxicity

Active Publication Date: 2018-07-31
SHANGHAI YUANSONG BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The five-year survival rate of pancreatic cancer patients is less than 5%. The reason is that its onset is hidden and there is no effective diagnostic method in the early stage. Due to the particularity of the anatomical structure and location of the pancreas, patients in the advanced stage often lose the opportunity for effective surgical treatment.
PKM2 (pyruvate kinase subtype 2), as the rate-limiting enzyme in the glycolysis process, plays an important role in the development of cancer and has become a hot spot in cancer metabolism research, but its role in pancreatic cancer has been less reported

Method used

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  • Cancer-targeting recombinant oncolytic gene-adenovirus and construction method and application thereof
  • Cancer-targeting recombinant oncolytic gene-adenovirus and construction method and application thereof
  • Cancer-targeting recombinant oncolytic gene-adenovirus and construction method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Recombinant oncolytic gene of the present invention-adenovirus Onco Ad The construction method of .RGD.shPKM2 is as follows:

[0032] Step 1. Construction of pShuttle-pSur-E1A-ΔE1B

[0033] The pShuttle plasmid pair pZd55-AFP-E1A-ΔE1B (Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression. Cancer Gene Ther 2012, 19(9):619-629) was digested with XhoI and SnaBI to recover large fragments; primer pssp was designed to pShuttle-pSur-△24-△E1B (Xu HN, Huang WD, Cai Y, Ding M, Gu JF, Wei N, Sun LY, Cao X, Li HG, Zhang KJ, Liu XY (2011).HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy. Mol Cancer 10,133.) as The template was amplified by PCR to obtain the survivin promoter, the PCR product was digested with XhoI and SnaBI, the fragment was recovered and ligated with the large fragment, transformed, and the...

Embodiment 2

[0046] Example 2 Recombinant Oncolytic Gene-Adenovirus Onco Ad .RGD.shPKM2 cytotoxicity test

[0047] The recombinant oncolytic gene-adenovirus O obtained in Example 1 Ad .R.shPKM2 and empty virus Onco Ad (hereinafter referred to as O Ad ), Onco Ad .RGD (hereinafter referred to as O Ad .R), for cytotoxicity experiments. o Ad , O Ad .R is an empty virus, as a control group, its construction method and the O of embodiment 1 Ad .R.shPKM2 is constructed in the same way (eg figure 1 As shown), its anticancer effect is only produced by oncolytic virus without therapeutic gene, the purpose is to prove that the anticancer effect of gene-loaded oncolytic virus is better than that of empty virus.

[0048] Crystal violet and cck-8 were used to verify the cytotoxic effect of recombinant oncolytic gene-adenovirus on pancreatic normal cells, pancreatic cancer cells, breast cancer cells MCF-7 and bladder cancer cells T24. The operation steps of crystal violet and cck-8 are conventi...

Embodiment 3

[0060] Example 3 Recombinant Oncolytic Gene-Adenovirus Onco Ad .RGD.shPKM2 inhibits the growth of PANC-1 cell xenograft tumor in nude mice

[0061] The recombinant oncolytic gene-adenovirus O obtained in Example 1 Ad .R.shPKM2 and empty virus O Ad , O Ad .R experiment of inhibiting the growth of xenografted tumor in nude mice.

[0062] The operation steps of the experiment of inhibiting the growth of xenografted tumors in nude mice are routine techniques in the art, for details, please refer to this document——Yang Y, Xu H, Shen J, Yang Y, Wu S, Xiao J, Xu Y, Liu XY and Chu L.RGD -modified oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells. Cell death & disease. 2015;6:e1760. All experiments were repeated three times.

[0063] in: Figure 6 (A) means O Ad .R.shPKM2 inhibited the growth of PANC-1 cell transplanted tumor in nude mice significantly higher than that of empty virus O Ad , O Ad .R; Figure 6 (B) is a photo...

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Abstract

The present invention discloses a group of cancer-targeting recombinant oncolytic gene-adenovirus, comprising OncoAd, OncoAd. RGD, and OncoAd. RGD. shPKM2. The invention also discloses a constructionmethod and application of the recombinant oncolytic gene-adenovirus OncoAd. RGD. shPKM2 in preparing of a medicine for treating pancreatic cancer. The recombinant oncolytic gene-adenovirus OncoAd. RGD. shPKM2 can achieves silencing of expression of rate-limiting enzyme gene PKM2 by means of replication of an adenoviral vector, and can play an effective pancreatic cancer killing effect.

Description

technical field [0001] The invention relates to the technical field of oncolytic adenovirus, in particular to a cancer-targeting recombinant oncolytic gene-adenovirus and its construction method and application. Background technique [0002] Pancreatic cancer is the most malignant solid tumor. According to the global cancer ranking statistics, the incidence of pancreatic cancer ranks tenth in men and ninth in women, but its mortality rate ranks third. The incidence and mortality of pancreatic cancer are increasing year by year. According to the statistics of the United States, by 2030, the death rate of pancreatic cancer will occupy the second place in the death rate of all cancers. The five-year survival rate of patients with pancreatic cancer is less than 5%. The reason is that its onset is hidden and there is no effective diagnostic method in the early stage. Due to the particularity of the anatomical structure and location of the pancreas, patients in the advanced stage ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N7/01C12N15/113C12N15/861A61K48/00A61P35/00C12R1/91
CPCA61K48/005C12N7/00C12N15/1137C12N15/86C12N2310/14C12N2710/10021C12N2710/10032C12N2710/10043
Inventor 刘新垣徐燕妮章康健顾锦法倪爱民方先龙
Owner SHANGHAI YUANSONG BIOTECHNOLOGY CO LTD
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