Modified Aptamer EGFR Binding Nuclease Resistance
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Solution Overview
Problem
Current aptamers used for targeting EGFR in cancer treatment are prone to degradation and have limited binding efficacy, which hampers their therapeutic effectiveness in targeting cancer cells.
Innovation Solution
Development of a ribonucleic acid molecule with a specific nucleotide sequence, incorporating 2'-O-methyl and 2'-fluoro substitutions, which enhances binding to EGFR and provides stability against nuclease degradation, combined with an immunogenic molecule to redirect the immune response to cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natural RNA aptamers are used to bind EGFR, then binding capability is achieved, but nuclease degradation occurs reducing therapeutic effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of RNA nucleotides through 2'-O-methyl and 2'-fluoro substitutions. These chemical modifications alter the physical and chemical parameters of the RNA backbone, conferring resistance to nuclease degradation while preserving the aptamer's ability to bind EGFR with high affinity
Solution Approach 2:
The patent creates composite materials by combining modified nucleotides (2'-O-methyl and 2'-fluoro substituted) with natural RNA sequences. This composite approach integrates the stability of modified nucleotides with the binding functionality of natural RNA aptamer sequences, achieving both durability and efficacy
2Reliability
If aptamers are used for cancer targeting, then specific binding to EGFR is achieved, but immune system evasion limits therapeutic impact
Solution Approach 1:
The patent merges two distinct functionalities into a single molecular construct: the EGFR-targeting aptamer domain and the immune-stimulating alpha-Gal epitope domain. This merging creates a bifunctional molecule that simultaneously achieves precise cancer cell targeting and active immune system engagement, transforming the aptamer from a passive binder to an active immunotherapeutic agent
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 modified aptamer effectively binds to EGFR-expressing cells, offering improved therapeutic potential by enhancing immune targeting of cancer cells while resisting degradation, thus providing a promising approach for cancer treatment.
Implementation Method 1
Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule
Implementation Method 2
incorporating 2'-O-methyl and 2'-fluoro substitutions, which enhances binding to EGFR and provides stability against nuclease degradation
Data Source
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AI summary
The invention relates to novel aptamers, in particular aptamers which are capable of binding to EGFR. The invention also relates to cancer cell binding complexes comprising said aptamers and the use of said cancer cell binding complexes in the treatment of cancer.