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

VSEngineering 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

Engineering Contradiction:
Improvechemical diversity of aptamersVSAvoidcomplexity of selection process
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

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.

Inventive Principle:
Principle #5Merging (Combining)

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.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Engineering Contradiction:
Improvespecificity and affinity of aptamersVSAvoidselection efficiency
Core Design Contradiction:
ReliabilityVSProductivity

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.

Inventive Principle:
Principle #5Merging (Combining)

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.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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

Engineering Contradiction:
Improveselection timeVSAvoidtechnical resources required
Core Design Contradiction:
Loss of timeVSDevice complexity

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.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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

Methodology Applied
Scientific EffectMolecular recognition:

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

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS20260022495A1Aptamer discovery and selection techniques
Publication Date: 2026.01.22 ILLUMINA INC
  • US20260022495A1 patent drawing
  • US20260022495A1 patent drawing
  • US20260022495A1 patent drawing

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.