Chem2Sense · Legonucleotides for detection

Sensors have a vital importance on human life, detecting diseases or contaminants that endanger the environment. A widely pursued challenge has been to develop universal biosensors with the flexibility to detect molecules regardless of their size. Antibodies have been used to fulfill this aim, but single-stranded oligonucleotides (aptamers) interact efficiently with targets and have also been proposed as an alternative. However, aptamers lack the ability for versatile functionalization to tune affinities, and they suffer from highly complex selection and identification. Chem2Sense proposes an interdisciplinary approach to overcome these obstacles. My hypothesis is that a new strategy based on the reversible conjugation of aptamers with small molecules will remove barriers in designing universal biosensors. Chem2Sense aims to redesign the aptamer concept with flexible oligolegonucleotides and a cutting-edge nanopore sequencing methodology. The two objectives will be to develop chemically modified nucleotides as lego-bricks to build high-affinity aptalegomers, and to develop a ground-breaking sequencing methodology using artificial intelligence to boost aptalegomer identification. The proposed legonucleotides are synthetic nucleotides that reversibly attach small molecules in a dynamic combinatorial library. After challenging a vast library against a target, a Darwinian chemical selection will occur, leading to the best fit, the aptalegomer, a high-affinity oligonucleotide of natural and conjugated legonucleotides.Therefore, the objective of Chem2Sense is to create a ground-breaking methodology that overcomes significant obstacles in aptamers’ development, providing a powerful synergy between novel chemical aptalegomers generation and a direct method for selection/identification using the latest advances in oligonucleotide sequencing. Chem2Sense will bring highly sensitive and versatile aptalegomers to a broad range of vital applications.