rAAV-shRNA Vector for Heart Failure Gene Therapy
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Solution Overview
Problem
Current gene therapy vectors for heart failure, such as adenovirus and lentivirus, have limitations like short expression time and immunogenicity, and there is a lack of effective small RNA drugs for treating heart failure in clinical practice.
Innovation Solution
Development of a recombinant adeno-associated virus (rAAV) vector delivering short hairpin RNA (shRNA) specifically targeting myocardial hypertrophy markers, which is designed to improve heart function and treat heart failure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If adenovirus or lentivirus are used as expression vectors for gene therapy, then gene expression can be achieved, but the expression time is short and immunogenicity occurs
Solution Approach 1:
The patent changes the vector type parameter from adenovirus/lentivirus to rAAV, which fundamentally alters the expression duration and immunogenicity characteristics. The rAAV vector provides long-term expression without significant immunogenicity, resolving the contradiction between expression duration and immunogenicity.
Solution Approach 2:
The patent uses rAAV as a copy of the viral vector system that inherits the delivery capability of adenovirus/lentivirus but avoids their limitations. The rAAV vector serves as a replicated version that maintains gene expression function while eliminating the short expression time and immunogenicity issues.
2Reliability
If conventional gene therapy vectors are used, then gene expression can be achieved, but they are not suitable for future clinical applications
Solution Approach 1:
The patent changes the vector parameters to rAAV, which provides long-term expression and low immunogenicity, making it suitable for future clinical applications. This parameter change transforms the vector from unsuitable for clinical use to highly suitable for future therapies.
3Measurement precision
If small RNA drugs are developed for heart failure treatment, then specific gene silencing can be achieved, but there is still a research gap in clinical practice
Solution Approach 1:
The patent uses rAAV as an intermediary delivery vehicle to transport shRNA to the target tissue. This intermediary system bridges the gap between laboratory gene silencing capability and clinical application, enabling precise delivery of therapeutic RNA to heart tissue.
Solution Approach 2:
The patent performs preliminary actions by optimizing the shRNA sequence (SEQ ID NO:1) and vector construction before clinical application. The preliminary development of the rAAV-shRNA-AHF system prepares the therapeutic agent for future clinical translation, addressing the research gap in heart failure treatment.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The rAAV-shRNA-AHF significantly improves cardiac function in animal models of heart failure, demonstrating potential as an effective anti-heart failure treatment.
Implementation Method 1
double stranded RNA or hairpin structure RNA (shRNA) can be cleaved by endonucleases to form siRNA
Implementation Method 2
forms RNA induced silencing complexes to cleave and degrade target gene, thereby inhibiting expression of target gene
Implementation Method 3
The recombinant adeno-associated virus vector (rAAV) overcomes shortcomings that other gene expression vectors cannot overcome, has no immunogenicity, and can drive a long-term expression of target genes in vivo
Data Source
AI summary
The present invention relates to a shRNA, its recombinant expression vector, transformant, anti-heart failure drug, preparation method, and use as drug thereof, belonging to a field of biomedicine. The present invention provides a shRNA whose DNA sequence is selected from a group consisting of SEQ ID NO. 1, SEQ ID NO. 3, and SEQ ID NO. 5. The present invention also provides a recombinant expression vector, transformant, anti-heart failure drug and its use as drug based on the shRNA, and provides a method for preparing the anti-heart failure drug. It's confirmed by animal experiments that the anti-heart failure drug provided by the present invention can significantly improve heart function of heart failure animals and play an effective anti-heart failure role.