@article{hemphill_liu_uprety_samanta_tsang_juliano_deiters_2015, title={Conditional Control of Alternative Splicing through Light-Triggered Splice-Switching Oligonucleotides}, volume={137}, ISSN={["0002-7863"]}, DOI={10.1021/jacs.5b00580}, abstractNote={The spliceosome machinery is composed of several proteins and multiple small RNA molecules that are involved in gene regulation through the removal of introns from pre-mRNAs in order to assemble exon-based mRNA containing protein-coding sequences. Splice-switching oligonucleotides (SSOs) are genetic control elements that can be used to specifically control the expression of genes through correction of aberrant splicing pathways. A current limitation with SSO methodologies is the inability to achieve conditional control of their function paired with high spatial and temporal resolution. We addressed this limitation through site-specific installation of light-removable nucleobase-caging groups as well as photocleavable backbone linkers into synthetic SSOs. This enables optochemical OFF → ON and ON → OFF switching of their activity and thus precise control of alternative splicing. The use of light as a regulatory element allows for tight spatial and temporal control of splice switching in mammalian cells and animals.}, number={10}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Hemphill, James and Liu, Qingyang and Uprety, Rajendra and Samanta, Subhas and Tsang, Michael and Juliano, Rudolph L. and Deiters, Alexander}, year={2015}, month={Mar}, pages={3656–3662} } @misc{liu_deiters_2014, title={Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach}, volume={47}, ISSN={["1520-4898"]}, DOI={10.1021/ar400036a}, abstractNote={Synthetic oligonucleotides have been extensively applied tocontrol a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson-Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanisms of biological processes, researchers need tools that allow for the perturbation of these processes with Nature's precision. Light represents an excellent external regulatory element since irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photolabile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photoregulation of DNA function. Using this approach, we have both activated and deactivated gene expression optochemically at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations.}, number={1}, journal={ACCOUNTS OF CHEMICAL RESEARCH}, author={Liu, Qingyang and Deiters, Alexander}, year={2014}, month={Jan}, pages={45–55} }