Chaserr-Targeting Nucleic Acid Therapy to Restore CHD2 Expression
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Solution Overview
Problem
CHD2 haploinsufficiency is associated with neurodevelopmental delay, intellectual disability, epilepsy, and behavioral problems, and existing treatments lack effective methods to increase CHD2 expression.
Innovation Solution
Introducing a nucleic acid agent that down-regulates the activity or expression of the human Chaserr lncRNA, specifically targeting its last exon, to increase CHD2 levels in neuronal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Chaserr lncRNA is present and active, then CHD2 expression is suppressed to maintain proper levels, but in CHD2 haploinsufficiency this suppression prevents adequate CHD2 expression increase
Solution Approach 1:
The invention converts the harmful suppressive effect of Chaserr lncRNA into a beneficial therapeutic target. By designing antisense oligonucleotides that specifically bind to Chaserr, the patent exploits the presence of this normally harmful element as the mechanism for therapy - neutralizing its suppression of CHD2 to restore adequate protein levels in haploinsufficient patients
Solution Approach 2:
The invention extracts or removes the harmful suppressive function of Chaserr lncRNA from the system. Using antisense oligonucleotides, the patent specifically targets and neutralizes Chaserr RNA molecules, effectively taking out its ability to suppress CHD2 expression and allowing therapeutic CHD2 levels to be achieved
2Quantity of substance
If antisense oligonucleotides target Chaserr to increase CHD2 levels, then CHD2 expression is improved, but specificity to avoid off-target effects is challenged
Solution Approach 1:
The invention applies local quality by designing antisense oligonucleotides with highly specific sequence complementarity to unique regions of the Chaserr lncRNA transcript. This localized specificity ensures that the therapeutic agent binds only to its intended target and not to other genomic elements, avoiding off-target effects while achieving the desired increase in CHD2 expression
3Quantity of substance
If Chaserr is lost or down-regulated, then CHD2 levels increase to compensate for haploinsufficiency, but uncontrolled increase may cause transcriptional interference
Solution Approach 1:
The invention applies partial action by using antisense oligonucleotides to achieve a controlled, partial down-regulation of Chaserr rather than complete elimination. This allows CHD2 levels to increase sufficiently to compensate for haploinsufficiency while avoiding the excessive increase that would cause transcriptional interference and harmful effects
Solution Approach 2:
The invention implements a feedback-controlled approach where antisense oligonucleotides modulate Chaserr levels to achieve a balanced increase in CHD2 expression. The therapeutic effect is self-regulating, increasing CHD2 to compensate for the missing allele while the remaining Chaserr function prevents overexpression and associated harmful transcriptional interference
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 method effectively increases CHD2 expression, potentially treating conditions such as intellectual disability, autism, and epilepsy by compensating for CHD2 haploinsufficiency.
Implementation Method 1
a nucleic acid agent that down-regulates activity or expression of human Chaserr, wherein the nucleic acid agent is directed at the last exon of human Chaserr
Data Source
AI summary
A method of increasing an amount of Chromodomain Helicase DNA Binding Protein 2 (CHD2) in a neuronal cell is provided. The method comprising introducing into the cell a nucleic acid agent directed at the last exon of human Chaserr, thereby increasing the amount of CHD2 in the neuronal cell.