Antisense Modulation of Aberrant Gene Expression in Precursor Cells

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current genetic disease therapies often focus on correcting the primary genetic defect but fail to address secondary effects caused by aberrantly expressed genes that are not directly related to the mutation, leading to incomplete symptom alleviation and limited treatment efficacy.

Innovation Solution

Modulating the expression of aberrantly expressed genes in precursor cells or directly in patients to normalize their levels, using anti-sense therapy, gene delivery vehicles, and compounds like anti-sense oligonucleotides or proteins to enhance cell differentiation and transplantation success, thereby addressing secondary disease aggravating effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current genetic disease therapies focus only on correcting the primary genetic defect, then the treatment approach remains simple and targeted, but secondary effects caused by aberrantly expressed genes are not addressed, leading to incomplete symptom alleviation

Engineering Contradiction:
Improvetreatment efficacyVSAvoidtherapy complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The therapy is segmented into two distinct components: (1) correction of the primary genetic defect through traditional gene therapy approaches, and (2) modulation of aberrantly expressed genes through antisense oligonucleotides or RNA interference. This segmentation allows each component to address specific aspects of the disease independently, improving overall treatment efficacy while maintaining clear therapeutic targets for each intervention.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention merges primary genetic defect correction with secondary aberrant gene expression modulation into a comprehensive therapeutic strategy. By combining these two approaches—using both traditional gene replacement/suppression and antisense/RNAi technology—the therapy addresses both the root cause and secondary effects of genetic diseases, thereby improving reliability without requiring entirely separate treatment protocols.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If aberrantly expressed genes are modulated to address secondary disease effects, then symptom alleviation is improved, but the treatment approach becomes more complex requiring additional therapeutic interventions

Engineering Contradiction:
Improvesymptom alleviationVSAvoidtherapeutic intervention complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Antisense oligonucleotides serve as intermediary molecules that specifically bind to aberrantly expressed mRNA transcripts, preventing their translation into harmful proteins. These oligonucleotides act as mediators between the therapeutic intervention and the target gene, enabling selective modulation of aberrant gene expression without affecting the primary genetic defect correction mechanisms, thus improving symptom alleviation with controlled complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The therapy utilizes parameter changes in gene expression levels by modulating the expression of aberrantly expressed genes through antisense oligonucleotides or RNA interference. By specifically targeting and reducing the expression levels of harmful aberrant genes while maintaining normal gene function, the treatment achieves better symptom alleviation through precise control of gene expression parameters without unnecessarily complicating the overall therapeutic approach.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If precursor cells are used for transplantation therapy, then the capacity to form new differentiated cells is enhanced, but the success of transplantation is limited by secondary effects of genetic defects in the precursor cells

Engineering Contradiction:
Improvecell differentiation capacityVSAvoidtransplantation success
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention applies preliminary action by modulating aberrantly expressed genes in precursor cells before transplantation into the patient. By using antisense oligonucleotides or RNA interference to correct secondary genetic effects ex vivo, the precursor cells are pre-conditioned to have improved differentiation capacity and reduced pathological features, thereby enhancing both productivity and reliability of the transplantation therapy when these corrected cells are introduced into the patient.

Inventive Principle:
Principle #10Preliminary 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 improves the capacity of precursor cells to differentiate into functional cells, alleviates symptoms, and enhances the success of cell transplantation therapy by correcting secondary effects of genetic defects, leading to improved muscle strength and quality of life for individuals with genetic muscular dystrophies and other genetic disorders.

Implementation Method 1

using anti-sense therapy, gene delivery vehicles, and compounds like anti-sense oligonucleotides or proteins to enhance cell differentiation

Methodology Applied
Scientific EffectAnti-sense binding: Absorption (physical)

Data Source

PatentEP2012813B1Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly or abnormally expressed gene
Publication Date: 2017.11.29 ACADEMISCH ZIEKENHUIS LEIDEN (H O D N LUMC)
  • EP2012813B1 patent drawingFigure 1A~1B
  • EP2012813B1 patent drawingFigure 1
  • EP2012813B1 patent drawingFigure 2

AI summary

The present invention provides means and methods for alleviating genetic disease. A genetic defect that has a phenotype in differentiated cells can lead to defects in precursor cells thereof. These so-called secondary defects contribute to the overall disease of the individual. In the present invention, genetic intervention with the aim to alleviate symptoms of genetic disease is directed toward the primary genetic defect in the differentiated cell and the secondary defect in the precursor cell.