Synthetic oligonucleotides have been extensively used in the control of a wide range of biological processes such as gene expression, gene editing, DNA replication, and protein activity. Based on well-established sequence design rules that rely on Watson–Crick base pairing interactions, the function of these oligonucleotides can be targeted to any gene of interest. In order to provide conditional control over oligonucleotide function, we are installing light-cleavable chromophore onto nucleobases and in phosphodiester backbones. This allows us to both activate and deactivate gene expression photochemically at the transcriptional and translational level with spatial and temporal control in human cells and zebrafish embryos. Specifically, we have developed caged triplex-forming oligonucleotides, DNA decoys, and plasmids to regulate transcription, and we have controlled translation with light-activated antisense agents and splice-switching oligonucleotides, and I will present the overall approach and select examples.

Optical control of nucleic acid function in biological systems

255th National Meeting (2018)

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