Preconference Session: NextGen Early Career Scientist Meeting Jonathan Watts Sunday, 13 October 10.05-10.35 The First Few Bases: Career and Chemical Modification Jonathan K. Watts RNA Therapeutics Institute, UMass Medical School, Worcester, MA, USA This plenary talk of the early career scientist symposium has been invited to be primarily about career trajectory and advice for trainee scientists. I will weave this information together with recent research results from my laboratory. In particular, this talk will describe some of our work on “tissue-specific medicinal chemistry” with a focus on optimization of antisense oligonucleotide chemistry for the lung and brain. Jonathan K. Watts, Ph.D. Associate Professor RNA Therapeutics Institute UMass Medical School 368 Plantation St., AS4.1051 Worcester, MA, 01609 USA
[email protected] 774-455-3784 25 Preconference Session: NextGen Early Career Scientist Meeting Ysobel Baker Sunday, 13 October 10.35-10.51 Backbone-modified locked nucleic acids for therapeutic antisense applications Ysobel Baker, Jinfeng Chen, Cameron Thorpe, Pawan Kumar, Afaf El-Sagheer, Tom Brown Department of Chemistry, University of Oxford Oligonucleotides with artificial backbones which mimic the natural phosphodiester linkage often show enhanced stability toward nucleases and have found applications in synthetic biology, nanotechnology, and gene synthesis. Whilst the incorporation of charge neutral analogues reduces the overall negative charge, these linkages typically reduce the thermal stability of the corresponding duplex, limiting their potential as therapeutics. In contrast, incorporation of conformationally restrained locked nucleic acid (LNA) into DNA improves the thermal stability of DNA:RNA duplexes. Therefore, we sought to combine the favourable properties of charge neutral linkages with those of LNA to create a new type of antisense oligonucleotide.