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Inactivated telomerase, adenovirus and artificial mRNA with same and application thereof

A technology of telomerase and adenovirus, which is applied in the fields of genetic engineering and cytology, can solve problems such as the inability to prevent transformation into cancer cells, and achieve the effect of preventing cell canceration and inhibiting cell death

Pending Publication Date: 2020-12-11
ZHEJIANG JUVENSIS THERAPEUTICS CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this non-specific design cannot eliminate the possibility that cells with mutations will transform into cancer cells with active telomerase

Method used

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  • Inactivated telomerase, adenovirus and artificial mRNA with same and application thereof
  • Inactivated telomerase, adenovirus and artificial mRNA with same and application thereof
  • Inactivated telomerase, adenovirus and artificial mRNA with same and application thereof

Examples

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Effect test

Embodiment

[0058] According to an exemplary embodiment of the present invention, adenovirus-inactivated telomerase AAV-CI-TERT is used to treat cardiac diseases.

[0059] By measuring the length of telomere tails in cardiac slices of patients with cardiomyopathy by immunofluorescence staining, it is found that patients with cardiomyopathy will have abnormal telomere shortening, which will gradually cause cell death and lead to disease progression and heart failure. Notably, no telomere shortening was detected in other biological samples from the patients. Experiments have found that this phenomenon can also be observed in cardiomyocytes differentiated from human stem cells, and the telomere length in the nucleus of cardiomyocytes differentiated from human stem cells can be measured by immunofluorescence staining, such as figure 2 , image 3 As shown, it is proved that cardiomyocytes differentiated from human stem cells can be used as an experimental model of abnormal telomere shortenin...

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Abstract

The invention discloses inactivated telomerase which is double mutation telomerase, and double mutation points of the inactivated telomerase are Y707F and D868A respectively. Also disclosed are adenovirus-inactivated telomerase and artificial mRNA-inactivated telomerase with double mutation points, and their use in the treatment of diseases associated with non-dividing cell telomere shortening. According to the present invention, the activity of the telomerase TERT in the non-dividing cell can be inhibited to become the inactivated telomerase CI-TERT while the telomerase is limited to leave the cell nucleus; the telomerase can be kept in a cell nucleus to protect the telomere tail end from being shortened, cell canceration caused by telomere lengthening due to the telomerase is prevented,the telomerase is kept in the cell nucleus to protect the telomere tail end under the condition that the canceration risk is reduced, and worsening of diseases caused by telomere shortening is inhibited.

Description

technical field [0001] The invention relates to the technical fields of genetic engineering and cytology. Specifically, it relates to an inactivated telomerase and its application. Background technique [0002] Telomere (Telomere) is a complex of multiple repeats of non-transcribed DNA (Deoxyribonucleic Acid deoxyribonucleic acid) and proteins at the end of human eukaryotic chromosomes. Studies have shown that telomeres are associated with aging, cell division control, and disease. Telomerase (Telomerase), an enzyme responsible for the extension of telomeres in cells, is a basic nuclear protein reverse transcriptase that can add telomere DNA to the end of eukaryotic chromosomes and fill the telomeres lost in DNA replication Together, the repair of telomeres can be lengthened so that telomeres are not lost due to cell division. [0003] In recent decades, gene therapy has gradually transformed from a scientist's dream to a reality. The carrier of gene therapy has always b...

Claims

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Application Information

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IPC IPC(8): C12N9/12C12N7/01A61K38/45A61K48/00A61P9/00A61P9/04A61P21/00
CPCC12N9/1276A61K48/005A61K48/0008A61P9/00A61P9/04A61P21/00C12Y207/07049A61K38/45C12N9/1241C12N15/86C12N2750/14143C12N2710/10343Y02A50/30A61K38/00A61K48/0016A61P25/00C12N2750/14141C12N7/00C12N2750/14122
Inventor 张家浩曾雪
Owner ZHEJIANG JUVENSIS THERAPEUTICS CO LTD
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