Antisense Oligonucleotide Targeting VEGF Polynucleotides

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for modulating VEGF expression and function in patient cells or tissues are inadequate, as they lack specificity and efficiency in targeting VEGF polynucleotides, leading to incomplete or ineffective regulation of VEGF-related diseases.

Innovation Solution

The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to a reverse complement of VEGF polynucleotides, which are administered to patient cells or tissues to modulate VEGF expression and function, either up-regulating or down-regulating its activity by binding to sense and/or antisense VEGF polynucleotides, including modified or substituted nucleotides and delivery methods such as subcutaneous, intramuscular, or intravenous administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods are used to modulate VEGF expression, then the approach is simple, but the specificity and efficiency of targeting VEGF polynucleotides is inadequate

Engineering Contradiction:

Improvespecificity of targeting VEGF polynucleotidesVSAvoidcomplexity of antisense oligonucleotide design and administration

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the VEGF polynucleotide into specific target regions (sense and antisense strands) and designs oligonucleotides that target specific segments of these regions. This segmentation allows for precise targeting of VEGF expression while managing complexity through focused design on specific genomic locations.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by designing oligonucleotides with specific sequence identities (at least 50% identity to reverse complement) targeted at specific locations within the VEGF polynucleotide. This localized approach ensures high specificity at the molecular level while the overall therapy protocol remains manageable.

Inventive Principle:

Principle #3Local quality

2Productivity

If conventional methods are used to modulate VEGF expression, then the treatment protocol is simple, but the efficiency of regulating VEGF-related diseases is incomplete

Engineering Contradiction:

Improveefficiency of regulating VEGF-related diseasesVSAvoidcompleteness of VEGF regulation

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs multi-functional oligonucleotides that can target both sense and antisense VEGF polynucleotides, thereby regulating VEGF expression through multiple mechanisms simultaneously. This universal approach enhances the efficiency and completeness of disease regulation compared to single-target methods.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The antisense oligonucleotides act as intermediary molecules that mediate between the therapeutic agent and the VEGF polynucleotide. By binding to specific regions of VEGF mRNA or pre-mRNA, these intermediaries enable efficient and complete regulation of VEGF expression, leading to improved disease outcomes.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Measurement precision

If antisense oligonucleotides are designed with high sequence identity to VEGF reverse complement, then the specificity of binding is improved, but the complexity of oligonucleotide design increases

Engineering Contradiction:

Improvespecificity of oligonucleotide binding to VEGFVSAvoidease of oligonucleotide design and synthesis

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent specifies that oligonucleotides need at least 50% sequence identity to the reverse complement of VEGF polynucleotides, rather than requiring 100% identity. This partial action approach achieves sufficient binding specificity while significantly simplifying the design and manufacturing process compared to perfect match requirements.

Inventive Principle:

Principle #16Partial or excessive action

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

This approach effectively modulates VEGF expression and function in patient cells or tissues, providing a targeted therapeutic strategy for VEGF-related diseases by specifically binding to VEGF polynucleotides, thereby addressing the limitations of existing methods.

Implementation Method 1

DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. Hybridization is also central to a variety of technologies that either detect a particular nucleic acid or alter its expression.

Methodology Applied

Scientific EffectHybridization:

Implementation Method 2

Antisense DNA has the added feature that DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H, an activity that is present in most cell types.

Methodology Applied

Scientific EffectRibonuclease H digestion:

Data Source

PatentUS9920322B2Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF

Publication Date: 2018.03.20 CURNA INC

AI summary

Oligonucleotide compounds modulate expression and/or function of Vascular Endothelial Growth Factor (VEGF) polynucleotides and encoded products thereof. Methods for treating diseases associated with Vascular Endothelial Growth Factor (VEGF) comprise administering one or more Oligonucleotide compounds designed to inhibit the VEGF natural antisense transcript to patients.