Multi-isoform HGF Gene Therapy for Cardiac Revascularization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current HGF gene therapy for cardiac conditions, particularly coronary artery disease (CAD), has shown mixed results, with most studies using only full-length HGF cDNA, and the effectiveness of deleted HGF cDNA remains unexplored, limiting the understanding of its therapeutic potential in treating CAD and promoting endothelialization.
Innovation Solution
Administering nucleotide sequences encoding multiple isoforms of hepatocyte growth factor (HGF), including full-length HGF, deleted variant HGF, NK1, NK2, and NK4, to treat incomplete revascularization of the myocardium and promote endothelial cell growth in blood vessels, thereby enhancing cardiac perfusion and preventing conditions like CAD and restenosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If only full-length HGF cDNA is used in gene therapy, then the therapeutic approach is simple and well-studied, but the therapeutic effectiveness is limited and inconsistent
Solution Approach 1:
The invention segments the HGF gene into multiple isoforms (full-length HGF, deleted HGF, and variant isoforms) and combines them in a single expression construct. This segmentation allows each isoform to contribute different functional properties, thereby improving therapeutic effectiveness while maintaining a unified gene therapy approach.
Solution Approach 2:
The invention merges multiple HGF isoforms into a single expression construct that can be delivered together. By combining full-length HGF, deleted HGF, and variant isoforms in one therapeutic composition, the patent achieves synergistic effects that improve revascularization and endothelialization outcomes compared to using any single isoform alone.
2Productivity
If multiple HGF isoforms are administered, then therapeutic effectiveness and endothelialization are improved, but the complexity of gene therapy increases
Solution Approach 1:
The invention creates a universal gene therapy construct that expresses multiple HGF isoforms simultaneously. This multi-functional approach allows a single therapeutic delivery system to achieve multiple outcomes: promoting angiogenesis, enhancing endothelialization, and improving revascularization, thereby increasing productivity without requiring multiple separate therapies.
Solution Approach 2:
The invention changes the parameter of HGF expression by introducing multiple isoforms with different functional characteristics. By varying the amino acid sequences and structural properties of HGF variants expressed from the gene construct, the patent optimizes the biological activity and therapeutic effectiveness of the gene therapy.
3Ease of manufacture
If deleted HGF cDNA is used, then the gene structure is simplified, but its therapeutic potential remains unexplored and unproven
Solution Approach 1:
The invention performs preliminary construction of the multi-isoform expression construct before clinical application. By pre-assembling the gene therapy composition containing full-length HGF, deleted HGF, and variant isoforms in the correct reading frames, the patent ensures that the deleted HGF cDNA contributes its intended therapeutic function rather than being a non-functional element.
Solution Approach 2:
The invention creates a composite gene therapy composition that integrates multiple HGF isoforms with different functional properties. This composite approach combines the advantages of full-length HGF (structural stability) with deleted HGF (simplified structure and potential enhanced activity) to achieve superior therapeutic effectiveness.
Data Source
Figure 1
Figure 1
Figure 2
AI summary
The present invention relates to methods for treating or preventing cardiac conditions in a subject comprising administering to the subject two or more isoforms of hepatocyte growth factor (HGF). The present invention further relates to methods for promoting endothelial cell growth in a blood vessel comprising administering to the blood vessel two or more isoforms of hepatocyte growth factor (HGF). In one embodiment the two or more isoforms of HGF are administered as one or more polynucleotides encoding the isoforms.