Non-radioactive Modified Nucleotides for Safe DNA Sequencing
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Solution Overview
Problem
The use of radioactively labeled nucleotides poses hazards due to radiation and has a short shelf life, necessitating the development of safer, chemically labeled alternatives for nucleic acid detection and isolation.
Innovation Solution
Nucleotides are modified at the 5 position of pyrimidine or the 7 position of purine to create non-disruptive probes that can be incorporated into DNA or RNA, allowing for non-disruptive tagging and detection using biotin or other markers, enabling efficient affinity probes for specific sequences without interfering with double helix formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If radioactively labeled nucleotides are used for nucleic acid detection, then detection capability is achieved, but radiation hazards and short shelf life occur
Solution Approach 1:
The patent extracts the harmful radioactive component from the labeling system and replaces it with non-radioactive chemical labels such as biotin, fluorophores, or other detectable moieties. This maintains the detection function while eliminating radiation hazards and shelf life limitations associated with radioactive decay.
2Reliability
If nucleotides are modified for detection labeling, then detection capability is improved, but interference with double helix formation may occur
Solution Approach 1:
The patent applies labeling modifications at specific, strategically chosen positions on the nucleotide structure (such as the base, sugar, or phosphate groups) rather than throughout the entire molecule. This localized modification approach ensures that the detection function is achieved while minimizing disruption to the nucleotide's ability to form and maintain stable double helix structures.
Data Source
AI summary
A process for determining the sequence of nucleic acids of interest employs nucleotides or nucleotide analogs that have been made detectable by non-radioactive modifying or labeling. Such nucleotides or nucleotide analogs are modified on the sugar moieties, the phosphate moieties or the base moieties, including base analogs. Modified nucleotide analogs can be attached to or coupled to or incorporated into DNA or RNA. The modified or labeled nucleotides or nucleotide analogs are also useful in processes for detecting the presence of nucleic acids of interest and for characterizing chromosomal sequences. Detection processes using the modified or labeled nucleotides or nucleotide analogs extend to the use of a gel for separating or resolving hybrids formed between non-radioactively labeled oligonucleotides or polynucleotides and such nucleic acids of interest.