Inactive telomerase, adenovirus associated virus and artificial mRNA having same and use thereof
View Patent ↗The present invention discloses an inactive telomerase, which is a double mutant telomerase having double mutation sites Y707F and D868A. The present invention also discloses an adenovirus-inactive telomerase and an artificial mRNA-inactive telomerase having double mutation sites, and use thereof in the treatment of diseases associated with non-dividing cell telomere shortening. The present invention is capable of inhibiting the activity of telomerase TERT in non-dividing cells to form an inactive telomerase CI-TERT and simultaneously preventing the telomerase from leaving the nucleus. By such configuration, the telomerase can be kept in the nucleus to protect the telomeric ends from shortening and prevent telomerase from causing telomere lengthening to the extent of cell carcinogenesis, thus reducing the risk of carcinogenesis and keeping the telomerase in the nucleus to protect the telomeric ends and inhibiting the deterioration of the disease caused by telomere shortening.
1 . An inactive telomerase, characterized in that said inactive telomerase is a double mutant human telomerase of which the two mutation sites are Y707F and D868A, respectively.
2 . An adeno-associated virus (AAV) vector, characterized in that the AAV vector expresses the inactive telomerase according to claim 1 .
3 . An artificial mRNA vector expressing the inactive telomerase according to claim 1 .
4 . A method of treating a disease associated with telomere shortening in non-dividing cells by administering the AAV vector according to claim 2 to a subject.
5 . The method according to claim 4 , characterized in that said non-dividing cells are selected from a cardiomyocyte, a skeletal muscle cell, or a nerve cell.
6 . The method according to claim 4 , characterized in that said disease associated with telomere shortening in non-dividing cells comprises diseases associated with telomere shortening in a cardiomyocyte.
7 . The method according to claim 6 , characterized in that said disease associated with telomere shortening in a cardiomyocyte is selected from a dilated cardiomyopathy (DCM), a hypertrophic cardiomyopathy (HCM), a nuclear fibrillar protein disease, or a telomere shortening-related rare heart disease.
8 . The method according to claim 7 , characterized in that said telomere shortening-related rare heart disease comprises Duchenne muscular dystrophy (DMD).
9 . A method of treating-a disease associated with telomere shortening in non-dividing cells by administering the artificial mRNA vector according to claim 3 to a subject.
10 . The method according to claim 9 , characterized in that said non-dividing cells are selected from a cardiomyocyte, a skeletal muscle cell, or a nerve cell.
11 . The method according to claim 9 , characterized in that said disease associated with telomere shortening in non-dividing cells comprises diseases associated with telomere shortening in a cardiomyocyte.
12 . The method according to claim 11 , characterized in that said disease associated with telomere shortening in a cardiomyocyte is selected a dilated cardiomyopathy (DCM), a hypertrophic cardiomyopathy (HCM), a nuclear fibrillar protein disease, or a telomere shortening-related rare heart disease.
13 . The method according to claim 12 , characterized in that said telomere shortening-related rare heart disease comprises Duchenne muscular dystrophy (DMD).