19th-banner-rev.gif

Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Regulation of Gene Expression with Programmable DNA Binding Oligomers

DNA binding polyamides are synthetic oligomers which mimic regulatory proteins and can be programmed to bind a large repertoire of DNA sequences (1, 2). Modified polyamides are cell permeable and shown to traffic to the nucleus (3). The integration of polyamides into the transcriptional machinery of living cells to control biological circuitry can be imagined by three different strategies. Interfere with regulatory proteins in the promoter of endogenous genes can result in gene silencing (4). Recruitment of the transcriptional machinery in promoters of specific genes can activate gene expression (5, 6). Target the coding region of genes by a covalent steric blockade inhibits polymerase elongation (7).

References and Footnotes
  1. S. White et al., Nature 391, 468 (1998).
  2. C. L. Kielkopf et al., Science 282, 111 (1998).
  3. B. S. Edelson et al., Nucl. Acids Res. 32, 2802 (2004).
  4. B. Olenyuk et al., Proc. Natl. Acad. Sci. USA 101, 16768 (2004).
  5. A. Z. Ansari et al., Chem. & Biol. 8, 583 (2001).
  6. Y. Kwon et al., J. Am. Chem. Soc. 126, 15940 (2004).
  7. L. A. Dickinson et al., Chem. & Biol. 11, 1 (2004).

Peter B. Dervan

Division of Chemistry & Chemical Engineering
California Institute of Technology
Pasadena, CA 91125

Phone: 626-395-6020
Fax: 626-683-8753
Email: dervan@caltech.edu