C5a-Binding Nucleic Acids for Stable Cross-Species Binding
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Solution Overview
Problem
Existing compounds targeting C5a or C5aR are prone to degradation and have fast clearance rates, limiting their effectiveness as drug-like molecules, and there is a need for a compound that interacts with both mouse and human C5a for disease treatment and diagnosis.
Innovation Solution
A nucleic acid molecule with specific nucleotide sequences capable of binding to human C5a, comprising central stretches of ribonucleotides and 2'-deoxyribonucleotides, and optionally flanked by terminal stretches, designed to interact with both mouse and human C5a.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds targeting C5a or C5aR are used, then C5a binding activity is achieved, but the compounds are prone to degradation and have fast clearance rates
Solution Approach 1:
The patent changes the chemical parameters of the binding compound by using nucleic acid molecules (DNA/RNA) instead of conventional small molecules or peptides. This parameter change results in improved stability and reduced degradation while maintaining C5a binding activity through complementary base pairing with the C5a receptor.
Solution Approach 2:
The invention employs composite material strategies by combining nucleic acid molecules with various chemical modifications and conjugations. These composite structures enhance the stability and pharmacokinetic properties of the C5a targeting compound while preserving its binding functionality.
2Reliability
If existing compounds targeting C5a or C5aR are used, then C5a binding activity is achieved, but clearance rates are fast
Solution Approach 1:
The patent changes the molecular size and chemical composition parameters by using nucleic acid molecules, which are larger and more stable than conventional drugs. This parameter change slows down renal clearance and extends the duration of action, allowing for prolonged C5a binding activity.
Solution Approach 2:
The invention avoids using short-living conventional drugs by employing nucleic acid molecules that can persist in the circulation longer. The nucleic acid-based compounds are designed to be metabolically stable, reducing frequent dosing requirements and extending therapeutic duration.
3Adaptability or versatility
If a compound is designed to interact with both mouse and human C5a, then cross-species compatibility is improved, but sequence specificity becomes more difficult to achieve
Solution Approach 1:
The patent applies universality by designing nucleic acid molecules with sequences that can bind to both mouse and human C5a receptors. The complementary DNA/RNA sequences are engineered to recognize conserved regions across species, enabling a single compound to function in both mouse models and human patients.
Solution Approach 2:
The invention uses local quality by focusing the binding sequence on specific conserved regions of the C5a receptor that are identical or similar across species. By targeting these locally conserved areas, the nucleic acid molecule achieves high specificity for the binding site while maintaining cross-species compatibility.
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 nucleic acid molecule effectively binds to C5a, providing a stable and effective means for treating and diagnosing diseases associated with C5a, while maintaining compatibility across species.
Implementation Method 1
A nucleic acid molecule with specific nucleotide sequences capable of binding to human C5a
Data Source
AI summary
The present invention is related to a nucleic acid molecule capable of binding to human C5a, wherein the nucleic acid molecule comprises a central stretch of nucleotides, wherein the central stretch of nucleotides comprises a nucleotide sequence of 5′ AUGn1GGUGKUn2n3RGGGHUGUKGGGn4Gn5CGACGCA 3′ [SEQ ID NO: 61], wherein n1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU and G, A, U, C, H, K, and R are ribonucleotides, and dU, dG and dA are 2′-deoxyribonucleotides.