Aptamer Selection Using DNA Shuffling and Computational SELEX
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Solution Overview
Problem
The current method of aptamer development, SELEX, is lengthy and expensive due to the production of large random libraries and time-consuming sequencing, making it inefficient for identifying aptamers with high specificity and affinity.
Innovation Solution
The recomSELEX method combines recombinatorial SELEX with a constrained genetic algorithm and computational SELEX to accelerate the aptamer identification process, incorporating DNA shuffling and molecular docking to optimize aptamers around a core sequence, reducing the number of selection rounds and enhancing specificity and affinity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard SELEX method is used to identify aptamers with high specificity and affinity, then the aptamers achieve desired binding properties, but the process becomes lengthy and expensive
Solution Approach 1:
The patent applies preliminary action by performing in silico counter-selection and molecular docking simulations before actual SELEX experiments. Computational methods pre-screen aptamer candidates to predict those with high affinity and specificity, eliminating low-quality candidates before wet lab work. This preliminary computational filtering reduces the number of experimental rounds needed while maintaining aptamer quality.
Solution Approach 2:
The patent uses computational copying by creating in silico models of aptamer-target interactions. Molecular docking simulations generate virtual copies of binding complexes to predict binding affinity without physical experimentation. This allows rapid evaluation of multiple aptamer sequences computationally before selecting candidates for actual SELEX, significantly reducing time and cost.
2Reliability
If standard SELEX method is used to identify aptamers with high specificity and affinity, then the aptamers achieve desired binding properties, but the cost of production increases
Solution Approach 1:
The patent replaces mechanical/wet lab systems with computational methods. Instead of performing multiple rounds of physical SELEX with cell culture, sequencing, and characterization, the invention uses in silico counter-selection and molecular docking algorithms to screen and evaluate aptamer candidates. This substitution of computational mechanics for physical experimentation dramatically reduces material costs, reagent consumption, and production expenses while maintaining aptamer quality.
Solution Approach 2:
The computational pipeline performs self-service by automatically evaluating aptamer candidates through in silico counter-selection and molecular docking without requiring extensive manual intervention. The system autonomously predicts binding affinities, filters candidates, and ranks sequences, reducing the need for repeated expensive wet lab experiments and manual sequencing efforts.
3Reliability
If standard SELEX method is used, then aptamers are identified through experimental screening, but the process requires numerous selection rounds and extensive cell culture
Solution Approach 1:
The patent replaces physical SELEX mechanics with computational algorithms. In silico counter-selection and molecular docking simulations enable rapid screening of large aptamer libraries without cell culture, PCR amplification, or physical separation steps. This substitution increases throughput dramatically while maintaining selection accuracy through rigorous computational filtering based on predicted binding thermodynamics and structural compatibility.
Data Source
AI summary
The present disclosure provides a novel approach, recomSELEX, that highly integrate mutually supportive recombination and computational methods for aptamer selection and identification. The recomSELEX approach comprises a recombinatorial SELEX platform for aptamer screening that exponentially increases the sequence space that is explored by incorporation of a DNA shuffling step that allows recombination between aptamers. Subsequently, the recombinatorial SELEX platform can also be employed to develop new and optimize already existing aptamers. The recomSELEX further comprises a computational SELEX platform with a constrained genetic algorithm (GA) to identify potential aptamers that are stable and have the desired specificity and affinity of a target.