DNA-Encoded Aptamer Libraries for High-Diversity SELEX Screening
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Solution Overview
Problem
Conventional SELEX methods for aptamer discovery face limitations due to restricted chemical diversity and inefficiencies in generating aptamers with high specificity and affinity for target molecules, requiring time-consuming and inefficient screening of multiple libraries.
Innovation Solution
Integration of DNA-encoded libraries with SELEX processes to generate aptamers with increased chemical diversity, allowing simultaneous screening of diverse modifications and identification of binding sequences through sequencing, thereby enhancing selection efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional SELEX methods are used for aptamer discovery, then the process is relatively simple to implement, but the chemical diversity of generated aptamers is restricted and selection efficiency is low
Solution Approach 1:
The patent combines DNA-encoded library technology with SELEX methodology to create an integrated aptamer discovery platform. The DNA-encoded library provides diverse modified nucleotides and sequences, while SELEX provides the selection framework, merging the strengths of both approaches to achieve high chemical diversity with systematic selection capability.
Solution Approach 2:
The patent creates a universal aptamer library platform that can screen for multiple different target molecules using a single library construction approach. The DNA-encoded framework with modified nucleotides serves multiple functions: providing sequence diversity, enabling target binding, and allowing high-throughput screening across different analytes simultaneously.
2Reliability
If multiple separate libraries are screened to find aptamers with high specificity and affinity, then comprehensive coverage of aptamer candidates is achieved, but the screening process becomes time-consuming and inefficient
Solution Approach 1:
The patent merges multiple aptamer candidate sequences with different modifications into a single DNA-encoded library, allowing simultaneous screening of all candidates against target molecules. This eliminates the need for sequential screening of separate libraries while maintaining comprehensive coverage of diverse aptamer candidates.
Solution Approach 2:
The patent adds the dimension of high-throughput sequencing to the traditional SELEX process. By encoding aptamer sequences in DNA and using next-generation sequencing, the system can analyze binding events across the entire library in parallel, transforming a sequential one-dimensional screening process into a parallel multi-dimensional analysis.
3Loss of time
If traditional aptamer selection methods are used, then the process requires fewer technical resources, but the production cost and time for obtaining high-quality aptamers increase
Solution Approach 1:
The patent replaces manual, step-by-step aptamer selection and characterization methods with automated DNA-encoded library screening coupled with high-throughput sequencing. This substitution of mechanical/manual processes with automated molecular and computational systems dramatically reduces selection time while managing technical resource requirements.
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
Facilitates high-throughput screening of aptamers with expanded chemical space, achieving high specificity and selectivity for target molecules with reduced selection cycles and lower production costs.
Implementation Method 1
Aptamers are nucleic acids that bind to molecular targets, such as proteins, with high affinity and specificity
Implementation Method 2
An individual at least partially single-stranded nucleic acid of the plurality includes a first conserved primer region that is conserved among the plurality of at least partially single-stranded nucleic acids; a second conserved primer region that is conserved among the plurality of at least partially single-stranded nucleic acids
Data Source
AI summary
Encoded aptamer candidate libraries with nucleotide modification are described. The aptamer candidates include a first conserved primer region and a second conserved primer region. aptamer candidates also include a variable region disposed between the first conserved primer region and the second conserved primer region and that includes at least one modified nucleotide. A code region includes a nucleotide sequence that is unique for a modification type of the at least one modified nucleotide such that a sequence of each aptamer candidate can be used to identify the associated modification type.


