Research Gene Regulation

Gene Regulation

The ability to sequence-specifically target double-stranded DNA is of great interest for the development of therapeutic drugs, diagnostic and experimental tools, and remains to be one of the most sought-after goals in modern chemistry and biology. Three approaches, triplex-forming oligonucleotides, helix-invading peptide nucleic acids (PNAs), and side-by-side minor-groove binders, have shown considerable promises; however, unresolved limitations in sequence specificity, target length, and cellular uptake still exist for all three approaches. Triplex-forming oligonucleotides and PNA are limited to homopurine targets, while side-by-side minor-groove binders are limited to short sequences; and all are not readily taken up by the mammalian cells. Our group is working to resolve these problems. The goal is to design a molecule that can be readily transported into the cells, and temporally and spatially regulated (to be able to sequence-specifically recognize and target ds-DNA and switch on/off at will).

Gene Targeting

Design and Synthesis of Photo-Switchable ds-DNA Binder

References
1. Denison, C & Kodadek, T., Chem. Biol., 5, R129 (1998).
2. Giovannaaangeli, C. & Helene, C., Antisense Nucleic Acid Drug Dev., 7, 413 (1997).
3. Nielsen, P. E., Egholm, M., Berg, R. H., Buchardt, O., Science, 254, 1497 (1991).
4. Nielsen, P. E, Acc. Chem. Res., 32, 624 (1999).
5. Gottesfeld, J. M., Neely, L., Trauger, J. W., Baird, E. E., Dervan, P. B., Nature, 387, 202 (1997).
6. White, S., Szewczyk, J. W., Turner, J. M., Dervan, P. B., Nature, 391, 468 (1998).