Targeted Oligonucleotide Aptamers for HNRPU Protein Binding
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Solution Overview
Problem
Current therapeutic options for diseases such as cancer lack specificity, stability, and efficient delivery mechanisms, particularly for targeting HNRPU proteins, which are critical for modulating cellular functions.
Innovation Solution
Development of oligonucleotide aptamers, including chemically modified sequences capable of binding to HNRPU proteins, which can inhibit nucleolin activity and induce apoptosis in cancer cells, and are designed for specific binding and internalization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional therapeutic options are used, then treatment can be administered broadly, but specificity for targeting HNRPU proteins is insufficient
Solution Approach 1:
The patent segments the therapeutic approach by using aptamers that specifically bind to HNRPU proteins, dividing the broad therapeutic target into specific molecular interactions. This allows selective targeting of HNRPU-containing complexes while sparing other cellular components, achieving high specificity through molecular segmentation rather than broad-spectrum action.
Solution Approach 2:
The aptamers exhibit local quality by concentrating their binding activity specifically at HNRPU protein sites within cellular complexes. The patent demonstrates that these aptamers achieve high local affinity (sub-nanomolar) at the target site while maintaining selective discrimination against closely related proteins, creating localized therapeutic effect with precise molecular recognition.
2Stability of the object's composition
If standard oligonucleotides are used, then synthesis is straightforward, but stability and resistance to degradation are insufficient
Solution Approach 1:
The patent employs composite oligonucleotide structures combining DNA and RNA segments with specific modifications. The aptamers contain 2'-O-methyl RNA modifications and phosphorothioate backbone modifications, creating composite materials that enhance nuclease resistance and serum stability while maintaining affinity for HNRPU proteins. These composite structures balance manufacturing feasibility with improved in vivo stability.
Solution Approach 2:
The patent applies parameter changes by modifying the chemical structure of oligonucleotides through 2'-O-methyl and phosphorothioate modifications. These parameter changes in sugar pucker, backbone charge, and flexibility enhance stability against degradation while preserving or improving binding affinity. The modifications alter physical-chemical parameters to achieve optimal stability-manufacturability balance.
3Measurement precision
If high affinity binding is achieved, then target recognition is improved, but delivery efficiency and cellular internalization are insufficient
Solution Approach 1:
The patent uses cell-penetrating peptide intermediaries conjugated to the aptamers to bridge the gap between high-affinity binding and cellular internalization. The TAT peptide or similar intermediaries facilitate endocytosis and cytoplasmic delivery of the aptamer-HNRPU complex, enabling the high-affinity aptamers to reach their intracellular targets efficiently without compromising their binding specificity.
Solution Approach 2:
The patent merges two functional components: the high-affinity binding aptamer and the cell-penetrating delivery vehicle. By combining these functions into a single conjugate system, the patent achieves both precise target recognition (through the aptamer portion) and efficient cellular internalization (through the peptide portion), resolving the contradiction between binding affinity and delivery efficiency.
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 aptamers provide high specificity and affinity for HNRPU proteins, enabling targeted cancer therapy with improved stability and delivery, leading to effective cytotoxicity and apoptosis induction in various cancer types.
Implementation Method 1
A series of structural studies have shown that aptamers are capable of using the same types of binding interactions (e.g., hydrogen bonding, electrostatic complementarity, hydrophobic contacts, steric exclusion) that drive affinity and specificity in antibody-antigen complexes.
Implementation Method 2
A series of structural studies have shown that aptamers are capable of using the same types of binding interactions (e.g., hydrogen bonding, electrostatic complementarity, hydrophobic contacts, steric exclusion) that drive affinity and specificity in antibody-antigen complexes.
Implementation Method 3
A series of structural studies have shown that aptamers are capable of using the same types of binding interactions (e.g., hydrogen bonding, electrostatic complementarity, hydrophobic contacts, steric exclusion) that drive affinity and specificity in antibody-antigen complexes.
Implementation Method 4
Development of oligonucleotide aptamers, including chemically modified sequences capable of binding to HNRPU proteins, which can inhibit nucleolin activity and induce apoptosis in cancer cells
Data Source
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AI summary
Methods and compositions are provided for oligonucleotides that bind targets of interest. The targets include cells and microvesicles, such as those derived from various diseases. The oligonucleotides can be used for diagnostic and therapeutic purposes. The target of the oligonucleotides can be a target such as PARP1, HIST1H1B, HIST1H1D, NCL, FBL, SFPQ, RPL12, ACTB, HIST1H4A, SSBP1, NONO, H2AFJ, and DDX21, or a complex, subunit or fragment thereof.