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Techniques and compositions for treating heart failure and ventricular remodeling by in vivo delivery of angiogenic transgenes

An angiogenesis and heart failure technology, applied in gene therapy, recombinant DNA technology, drug combination, etc., can solve problems such as insufficient transduction efficiency and transgene expression, incompetence, necrosis, etc.

Inactive Publication Date: 2000-09-20
RGT UNIV OF CALIFORNIA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, these reported methods suffer from one or more of the following deficiencies: insufficient transduction efficiency and transgene expression; pronounced immune responses to the vectors used including inflammation and tissue necrosis; Relative incompetence for transduction and transgene expression (i.e., gene transfer results in the transgene being delivered also to non-cardiac sites such as the liver, kidney, lung, brain and testis of the test animal)
However, these agents are only partially effective in preventing unwanted ventricular remodeling and new treatment options are needed

Method used

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  • Techniques and compositions for treating heart failure and ventricular remodeling by in vivo delivery of angiogenic transgenes
  • Techniques and compositions for treating heart failure and ventricular remodeling by in vivo delivery of angiogenic transgenes
  • Techniques and compositions for treating heart failure and ventricular remodeling by in vivo delivery of angiogenic transgenes

Examples

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Embodiment 1

[0144] Example 1 describes a model of heart failure induced by prolonged (3- to 4-week period) but rapid ventricular pacing. This example shows that in an animal model of heart failure, left ventricular myocardial blood flow is abnormally low when the left ventricle is dilated and signs of heart failure are present. In this model, myocardial demand often exceeds myocardial blood flow (oxygen supply) and results in myocardial ischemia.

Embodiment 2

[0145] Example 2 shows the construction of an adenoviral vector used in the present invention.

Embodiment 3

[0146] Example 3 describes preliminary in vitro experiments to establish the efficiency of the adenoviral vectors of the invention. A control (beta-galactosidase-encoding) adenoviral vector was also tested. This result shows that the recombinant adenovirus vector of the present invention can indeed infect mature cardiomyocytes and provide high-efficiency expression of the transgene. In vivo experiments were then performed.

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Abstract

Methods are provided for treating patients with congestive heart failure (including dilated cardiomyopathy and congestive heart failure associated with severe coronary artery disease), and for preventing or alleviating deleterious ventricular remodeling after myocardial infarction. The preferred methods of the present invention involve in vivo delivery of genes encoding angiogenic proteins or peptides to the myocardium by direct injection of a vector containing the gene into a blood vessel supplying the heart.

Description

[0001] A note about government-funded research [0002] Certain work described here was supported in part by US Government funding under Grant Nos. VA-HL0281201 and IP50HL53773.01 awarded by the National Institutes of Health. The US Government may have certain rights in this invention. field of invention [0003] The present invention relates to methods and compositions for treating cardiovascular disease. More specifically, the invention relates to techniques and polynucleotide constructs for the treatment of heart failure and ventricular remodeling by delivery of angiogenic transgenes in vivo. Background of the invention [0004] It has been reported that 3-4 million adults in the United States suffer from congestive heart failure (herein referred to simply as "CHF"); : 27-34, 1995). CHF is the most common required hospitalization (case) and 500,000 patients are diagnosed out of hospital each year in US hospitals. Once the symptoms of heart failure are moderately sever...

Claims

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Application Information

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IPC IPC(8): C12N15/09A61K35/76A61K38/18A61K48/00A61P9/00A61P9/04
CPCA61K38/1858A61K38/1866A61K38/1825A61K38/30A61K48/00A61P9/00A61P9/04
Inventor H·K·哈蒙德T·L·凯利
Owner RGT UNIV OF CALIFORNIA
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