BIOL 137 |
| Our lab is designing photoactive oligonucleotides with the goal of controlling in vivo gene expression with high spatial and temporal control. As proof-of-principle, DNA polymerase activity was modulated 25-fold using UV light. More recently, methods have been developed for controlling DNA and RNA hybridization. For example, hybridization of an antisense oligodeoxynucleotide (asODN) to a target mRNA can inhibit translation by sterically blocking the ribosome and/or recruiting endogenous ribonucleases. A series of light-activated DNA hairpins was synthesized by covalently attaching a 20-mer asODN to a complementary sense strand through a heterobifunctional photocleavable linker. The photoactive conjugates were stabilized by ~ 1-4 kcal/mole compared to the corresponding asODN/sODN duplexes. These differences in stability made it possible to regulate asODN/RNA duplex formation. In vitro RNase H assays showed 3-10-fold increases in RNA degradation upon photoactivation of the asODN/sODN hairpin. Experiments to photoregulate genes within leukemia cells, neurons, and zebrafish embryos will be described. |
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Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Division of Biological Chemistry |