Multi-Target Functional Nucleic Acids for Protein Translation Upregulation
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Solution Overview
Problem
Existing therapeutic approaches for genetic diseases characterized by multiple protein abnormalities, such as 22q.11.2 deletion syndrome, are limited to targeting single genes and often ineffective in addressing complex phenotypes.
Innovation Solution
Development of functional nucleic acid molecules comprising multiple target binding sequences and regulatory sequences, such as SINE B2 elements or IRES, to simultaneously upregulate the translation of multiple proteins of interest without affecting mRNA levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If single-target therapeutic approaches are used for genetic diseases, then treatment simplicity is maintained, but therapeutic effectiveness for complex diseases is insufficient
Solution Approach 1:
The patent creates a single functional nucleic acid molecule that performs multiple functions by incorporating multiple target binding sequences, each capable of binding to different mRNA targets. This multi-functional molecule can simultaneously upregulate translation of multiple proteins, making one therapeutic agent effective for complex diseases involving multiple gene defects, thereby resolving the contradiction between therapeutic effectiveness and molecule complexity
Solution Approach 2:
The patent merges multiple target binding sequences into a single functional nucleic acid molecule structure that includes regulatory sequences (SINE B2 or IRES). By combining multiple targeting capabilities within one molecule, the patent achieves simultaneous multi-protein upregulation, improving therapeutic effectiveness for complex diseases without requiring multiple separate therapeutic molecules
2Adaptability or versatility
If multiple single-target therapies are administered, then coverage of multiple genes is achieved, but treatment complexity and off-target effects increase
Solution Approach 1:
The functional nucleic acid molecule is designed with multiple target binding sequences that can simultaneously recognize and bind to different mRNA targets. This universal design allows a single molecule to provide multi-gene coverage, achieving the versatility of multiple therapies while maintaining the simplicity of a single treatment protocol and reducing off-target effects associated with multiple separate therapies
Solution Approach 2:
The patent combines multiple target binding sequences into one integrated functional nucleic acid structure with regulatory elements. This merging approach achieves multi-gene coverage through a single therapeutic agent, simplifying the treatment regimen and reducing the complexity associated with administering multiple separate single-target therapies
3Reliability
If protein translation is upregulated, then protein levels are restored to beneficial ranges, but mRNA levels remain unaffected limiting traditional therapeutic mechanisms
Solution Approach 1:
The functional nucleic acid molecule acts as an intermediary that specifically targets the translation process rather than mRNA stability or transcription. By incorporating regulatory sequences (SINE B2 or IRES) that interfere with translation initiation or elongation, the molecule restores protein levels to beneficial ranges through a novel mechanism that is flexible and adaptable for treating diseases caused by reduced protein expression
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 functional nucleic acid molecules effectively enhance the translation of multiple proteins, providing a therapeutic approach for complex genetic diseases by restoring protein levels to a physiologically beneficial range, thereby addressing the limitations of single-target therapies.
Implementation Method 1
functional nucleic acid molecules comprising two or more target binding sequences and a regulatory sequence comprising a SINE B2 element or an internal ribosome entry site (IRES)... methods of enhancing protein translation
Implementation Method 2
a regulatory sequence comprising a SINE B2 element or an internal ribosome entry site (IRES)... IRES upregulate target protein levels by promoting translation initiation
Implementation Method 3
The BD overlaps with the sense transcript and through base complementarity, determines SINEUP specificity... each target binding sequence comprises a sequence reverse complementary to a target mRNA sequence
Data Source
AI summary
The present invention relates to functional nucleic acid molecules comprising two or more target binding sequences and a regulatory sequence comprising a SINE B2 element or an internal ribosome entry site (IRES). The invention also encompasses methods of enhancing protein translation efficiency, and methods of treating gene defects using the functional nucleic acid molecules of the invention.