The genetics of SELEX

Abstract

SELEX is a robust technique for identifying nucleic acid aptamers with selectable characteristics. SELEX is a combinatorially tedious exhaustive search system, typically involving up to 1010 possible aptamers. Fully understanding functional relationship(s) between sequence and binding for each SELEX round would be prohibited by the sheer quantity of information. This leaves somewhat of an unknown as to the specific interactions that take place during a particular SELEX round, what the optimal conditions for aptamer evolution are, and additionally how SELEX could be improved upon. Here, using VB.net we have designed and scripted a computer program, “AptSim”, which simulates aptamer mutation, recombination and selection. AptSim demonstrates the value of an extended SELEX approach that exploits both mutation and recombination. It can also be used to find optimal strategies for maximising the rate of evolution, sometimes dramatically reducing the size, time span and/or cost of developing effective aptamers. Using AptSim, optimisation of SELEX experiments can be performed with increased speed and reduced cost when compared to a purely wet lab approach. In addition it may be possible to evaluate theoretical advancements to the SELEX technique which could lead to improvement of ligand evolution.