Multivalent Nucleotide Constructs for Uniform DNA Sequencing
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Solution Overview
Problem
Existing DNA sequencing technologies face challenges in achieving uniform coverage and efficiency, necessitating the development of improved sequencing reagents such as modified nucleotides and nucleotide constructs.
Innovation Solution
The development of multivalent nucleotide constructs with specific moieties and linkers, including nucleotide, fluorescent, and bioconjugate-reactive moieties, to enhance sequencing efficiency and uniformity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional nucleotides are used in DNA sequencing, then the sequencing process can be performed, but uniform coverage and efficiency are not achieved
Solution Approach 1:
The nucleotide construct is divided into distinct functional segments: a nucleotide moiety for sequencing, a fluorescent moiety for detection, and a bioconjugate-reactive moiety for attachment. This segmentation allows each component to be optimized independently, improving both sequencing efficiency and coverage uniformity
Solution Approach 2:
The nucleotide construct integrates multiple functions into a single molecule: it serves as a sequencing reagent, carries a fluorescent label for detection, and includes bioconjugate-reactive groups for attachment to biomolecules. This multi-functionality resolves the contradiction by achieving improved productivity and precision simultaneously
2Productivity
If modified nucleotides are developed to improve sequencing, then efficiency and uniformity improve, but the complexity of the nucleotide construct increases
Solution Approach 1:
Multiple functional components (nucleotide moiety, fluorescent moiety, bioconjugate-reactive moiety) are merged into a single nucleotide construct through covalent linkers. This merging achieves improved sequencing efficiency while managing complexity by integrating functions rather than using separate components
Solution Approach 2:
The nucleotide construct is a composite molecule combining different chemical moieties with specific functions. Each moiety is designed with appropriate chemical properties, and the composite structure achieves synergistic effects that improve sequencing efficiency without excessive complexity
Data Source
AI summary
Disclosed herein, inter alia, are multivalent nucleotide constructs and methods for making and using such constructs.