saRNA Compositions Targeting Sense Transcripts for Gene Up-regulation

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Solution Overview

Problem

Current methods for modulating gene expression using small activating RNAs (saRNAs) often require prior identification of antisense transcripts or interaction with polycomb complexes, limiting their application in diagnostic and therapeutic contexts.

Innovation Solution

Development of saRNA compositions that target antisense RNA transcripts of target genes, allowing for the up-regulation of specific genes without the need for a priori identification of antisense transcripts or reliance on polycomb complex interactions, using single-stranded or double-stranded RNAs with high complementarity to modulate gene expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current methods using small activating RNAs (saRNAs) are employed to modulate gene expression, then gene expression can be up-regulated, but prior identification of antisense transcripts or interaction with polycomb complexes is required, limiting application versatility

Engineering Contradiction:
Improvegene expression modulation effectivenessVSAvoidapplication versatility in diagnostic and therapeutic contexts
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention extracts and eliminates the requirement for prior identification of antisense transcripts and polycomb complex interactions from the saRNA methodology. By designing saRNAs that directly target sense mRNA transcripts without needing pre-identified antisense partners or polycomb complex engagement, the method removes these limiting dependencies while maintaining gene up-regulation effectiveness

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates a universal saRNA platform that can be applied across diverse diagnostic and therapeutic contexts without requiring context-specific adaptations or pre-identification steps. The methodology works with any target gene by designing saRNAs complementary to the gene's sense transcript, making it broadly applicable rather than limited to specific polycomb-associated genes

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If prior identification of antisense transcripts is required for saRNA design, then specific gene targeting can be achieved, but the process complexity and time requirements increase

Engineering Contradiction:
Improvetarget gene identification accuracyVSAvoidmethodological complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Instead of identifying antisense transcripts and then designing saRNAs to target them (the conventional approach), the invention inverts the logic by directly designing saRNAs complementary to the sense mRNA transcript of the target gene. This inversion eliminates the need for antisense transcript identification while maintaining precise target gene specificity through direct complementarity design

Inventive Principle:
Principle #13The other way round (Inversion)

3Adaptability or versatility

If saRNA compositions are designed to target antisense RNA transcripts, then therapeutic applications can be enabled, but the design process requires a priori identification of antisense transcripts which limits productivity

Engineering Contradiction:
Improvetherapeutic application capabilityVSAvoiddesign and development speed
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The invention performs preliminary action by directly designing saRNAs complementary to the sense transcript sequence, which is readily available from standard genomic databases. This eliminates the need for preliminary antisense transcript identification experiments, thereby accelerating the design and development process while maintaining therapeutic application capability

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

The saRNA compositions effectively up-regulate target gene expression, enabling therapeutic and diagnostic applications by directly targeting antisense RNA transcripts, thereby increasing gene expression levels and promoting cellular proliferation.

Implementation Method 1

single-stranded or double-stranded RNAs with high complementarity to modulate gene expression

Methodology Applied
Scientific EffectComplementary base pairing: Chemical Bonding

Data Source

PatentEP3286318A2Sarna compositions and methods of use
Publication Date: 2018.02.28 MINA THERAPEUTICS

AI summary

The invention relates to oligonucleotides, e.g., saRNAs useful in upregulating the expression of a target gene and therapeutic compositions comprising such oligonucleotides. Methods of using the oligonucleotides and the therapeutic compositions are also provided.