Generation of DNA Oligomers with Similar Chemical Kinetics via In-Silico Optimization

Abstract

Abstract Networks of interacting DNA oligomers are useful for applications such as biomarker detection, targeted drug delivery, information storage, and photonic information processing. However, differences in the chemical kinetics of hybridization reactions, referred to as kinetic dispersion, can be problematic for certain applications. Here, it is found that controlling known factors is sufficient to mitigate most kinetic dispersion. Eliminating complementary base-sequences which are not part of the desired hybridization reaction, referred to as unnecessary duplexes, is key to achieving exceptionally low kinetic dispersions. An analysis of existing experimental data indicates that unnecessary duplexes explain up to 94% of previously reported kinetic dispersion. Nearly all networks are found to contain unnecessary duplexes substantial enough to affect hybridization kinetics. New networks are generated using in-silico optimization, reducing in-vitro kinetic dispersion up to 86%. Limitations of the generation method are tested by creating oligomers for three previously programmed reactions and one previously engineered structure.