Antisense Oligonucleotides Targeting HGF Natural Antisense Transcripts

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Solution Overview

Problem

Current methods for modulating the expression and function of Hepatocyte Growth Factor (HGF) are limited in their ability to specifically target and regulate HGF polynucleotides, leading to inefficiencies in therapeutic applications.

Innovation Solution

The use of antisense oligonucleotides, specifically designed to target natural antisense transcripts of HGF, which are 5 to 30 nucleotides in length and have at least 50% sequence identity to specific regions of HGF polynucleotides, to modulate the expression and function of HGF in patient cells or tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods are used to modulate HGF expression, then the approach is simple, but the specificity and effectiveness of targeting HGF polynucleotides is insufficient

Engineering Contradiction:

Improvespecificity of HGF targetingVSAvoidcomplexity of antisense oligonucleotide design

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The invention segments the HGF polynucleotide into specific target regions (5 to 30 consecutive nucleotides) and designs corresponding antisense oligonucleotides to target each segment. This segmentation enables precise localization and modulation of HGF expression at specific genomic locations, resolving the contradiction between targeting specificity and method simplicity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by designing antisense oligonucleotides with specific sequence identity (at least 50%) to specific regions of HGF polynucleotides. This allows differential modulation of HGF expression at different genomic locations, achieving high specificity while maintaining a relatively simple overall approach.

Inventive Principle:

Principle #3Local quality

2Productivity

If antisense oligonucleotides are used to target natural antisense transcripts, then HGF expression can be effectively modulated, but the complexity of the therapeutic approach increases

Engineering Contradiction:

Improveeffectiveness of HGF modulationVSAvoidcomplexity of antisense oligonucleotide therapy

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The invention extracts the natural antisense transcript of HGF as a specific target and designs antisense oligonucleotides to complement and inhibit this extracted sequence. By isolating and targeting the antisense transcript specifically, the therapy achieves effective HGF modulation while managing complexity through focused targeting rather than broad-spectrum approaches.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of directly targeting the HGF sense transcript for suppression, the invention takes an inverted approach by targeting the natural antisense transcript. This inversion strategy modulates HGF expression indirectly through antisense oligonucleotide binding to the antisense strand, achieving therapeutic effectiveness while simplifying the overall therapeutic mechanism.

Inventive Principle:

Principle #13The other way round (Inversion)

3Measurement precision

If antisense oligonucleotides with high sequence identity are designed, then targeting precision is improved, but the difficulty of detecting and measuring target binding increases

Engineering Contradiction:

Improveprecision of target bindingVSAvoiddifficulty of detecting oligonucleotide binding

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The invention optimizes the sequence identity parameter to at least 50% for the antisense oligonucleotides to ensure sufficient binding precision. By setting this specific parameter threshold, the invention achieves effective target recognition while maintaining measurability of binding events, resolving the contradiction between precision and detectability.

Inventive Principle:

Principle #35Parameter changes

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 up-regulates or down-regulates HGF expression, as demonstrated by increased HGF mRNA levels in treated cells, offering a targeted therapeutic mechanism for HGF-related disorders.

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

PatentUS8940708B2Treatment of hepatocyte growth factor (HGF) related diseases by inhibition of natural antisense transcript to HGF

Publication Date: 2015.01.27 CURNA INC

AI summary

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Hepatocyte Growth Factor (HGF), in particular, by targeting natural antisense polynucleotides of Hepatocyte Growth Factor (HGF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of HGF.