EqualMESS - Equal Median Entropy in Structured Synthesis

DNA and RNA (nucleic acids) are the foundational molecules of life and some of the most basic elements of cell biology are carried out thanks to complementarity between DNA or RNA sequences. Complementarity means that a DNA sequence is the complement of another, its sequence of letters, taken from the genetic alphabet (ACGT, or ACGU for RNA), corresponds or complements the other sequence. If the first sequence, the first DNA molecule, starts with an A letter, then the complementary DNA sequence the second DNA molecule must have a T. For any C, the complement must have a G, and vice versa. This complementarity essentially becomes a reading tool through which DNA is copied, and RNA and proteins are made, but the structure and function of DNA and RNA has been shown to go well beyond this simple role. DNA and RNA molecules can be so structured, in a chemical sense, that they can bind other molecules that are not nucleic acids, much like what proteins and enzymes can do. They can also perform chemical reactions. This family of nucleic acids are called aptamers. They are sequences of ACGT still, but they assemble into tridimensional shapes that allow them to recognize and bind a target molecule. They have enormous potential in diagnostics and in medicine. They are much simpler and cheaper to synthesize than proteins, are much more stable and are more readily modifiable, which gave the moniker of chemical antibodies. The experimental process through which aptamers are discovered is called SELEX and, simply speaking, this process takes a very large amount of random DNA sequences and places this pool in presence of the target molecule. Through a process of careful selection, only the best DNA sequences, those which bind the target with the highest strength, are kept. SELEX was a revolution, but the technique suffers from severe limitations, such as low success rate, cumbersome methods of sequence identification, and is limited to DNA and RNA with little room for chemical modifications. In this project which we coined EqualMESS, we want to develop a more powerful alternative to SELEX for aptamer identification. We would grow libraries of nucleic acids, DNA, RNA or any type of chemically modified variant using a process called microarray photolithography. By adapting the synthesis process itself we aim to massively increase the library size and to perform a single binding assay in order to immediately identify a family of potential aptamers. With EqualMESS, we believe we can find novel aptamers in fewer steps than SELEX, with a higher success rate and with the possibility of modifying the chemical structure at will, and without any need for sequencing.