Use of RyR2 protein or RyR2 recombinant protein in preparation of anti-heart failure drug

A recombinant protein, heart failure technology, applied in drug combinations, peptide/protein components, recombinant DNA technology, etc.

Active Publication Date: 2018-12-18
PHARCHOICE THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the current drug treatment has played a certain role in controlling the disease symptoms and mortality of heart failure, it cannot fundamentally reverse the disease development, and 50% of heart failure patients will die within 5 years

Method used

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  • Use of RyR2 protein or RyR2 recombinant protein in preparation of anti-heart failure drug
  • Use of RyR2 protein or RyR2 recombinant protein in preparation of anti-heart failure drug
  • Use of RyR2 protein or RyR2 recombinant protein in preparation of anti-heart failure drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1. Effects of Myocardium-Specific Exogenous Expression of RyR2 Protein on Cardiac Function in Normal Small Animal Models

[0059] In order to detect the enhancement effect of AAV9-mediated RyR2cDNA myocardial gene transfer on cardiac function, 6-month-old normal C57B / 6 mice were divided into treatment group and control group. The intracellular delivery of all RyR2 recombinant proteins uses pAAV vectors, and FLAG tags are added to the C-terminus for easy detection. The viral vector construction diagram is as follows figure 1 . The polynucleotide encoding the following recombinant protein is the recombinant protein region of the carrier as shown in the figure, and the ATG start codon is added at the 5' end if necessary. The specific groups are as follows:

[0060] The CTRL control group is the empty virus group; the rSPRY1 group is the recombinant SPRY domain protein group, namely figure 1 The polynucleotide of the recombinant protein region of the vector show...

Embodiment 2

[0065]Example 2. Effects of Myocardium-Specific Exogenous Expression of RyR2 Protein on Cardiac Function in Small Animal Disease Models

[0066] Further, to evaluate the effect of AAV9-mediated RyR2cDNA myocardial gene delivery on cardiac function enhancement in disease models, the steps are as follows:

[0067] First, a 6-month-old C57B / 6 mouse myocardial infarction model was established. The model was established by temporarily occluding the left anterior coronary artery, referring to the non-patent literature Brinks et al.Circ Res (2010) 107:1140-1149; then, the The mice were divided into a treatment group and a control group. All RyR2 protein C-terminals were tagged with FLAG to facilitate detection. The specific construction method was the same as in Example 1. The virus cardiomyocyte infection technique, the construction of the virus vector and the method of using the myocardial specific promoter are the same as before, and the injection dose of the virus particles is 1×...

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Abstract

The invention relates to the technical field of biomedical engineering and provides a use of a RyR2 protein or a RyR2 recombinant protein in preparation of an anti-heart failure drug. The RyR2 recombinant protein is a fragment or a mutant of a natural RyR2 protein, such as a SPRY1 structural domain protein, a P1 structural domain protein, a SPRY2 structural domain protein, a SPRY3 structural domain protein, a Handle structural domain protein, a HD1 structural domain protein, a HD2 structural domain protein, a central structural domain protein, an EF-hand structural domain protein, a U-type motif protein, a P2 structural domain protein, a P2 structural domain fragment protein 1, a P2 structural domain fragment protein 2 or a P2 mutant of the natural RyR2 protein. The exogenous RyR2 recombinant protein has a high expression level in normal small animal models and small animal disease models so that the left ventricular ejection fractions of the experimental animals are increased to different extents compared with the control group, the disease model animals are able to reduce the beta-adrenergic-induced ventricular tachyarrhythmia to varying degrees and the ventricular function of each treatment group is recovered to varying degrees.

Description

technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to a type II ryanodine receptor (Ryanodine Receptor 2, RyR2) recombinant protein for enhancing the contractility of cardiomyocytes, a polynucleotide sequence encoding the RyR2 recombinant protein, and a carrier comprising the same and medicines and their uses. Background technique [0002] Heart failure is the terminal stage of most heart diseases and one of the main causes of human morbidity and mortality, and the incidence of heart failure is increasing worldwide. Although the current drug treatment has played a certain role in controlling the symptoms and mortality of heart failure, it cannot fundamentally reverse the disease development, and 50% of heart failure patients will die within 5 years. At the cellular level, heart failure mainly manifests as abnormal contraction and abnormal rhythm of cardiomyocytes. [0003] Muscle tissue can be divided into skeletal ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P9/04C07K14/705
CPCA61K38/177A61P9/04C07K14/705A61K38/1709C12N15/86
Inventor 胡适傅文燕
Owner PHARCHOICE THERAPEUTICS INC
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