Faculty

STANLEY T. CROOKE

• Chairman of the Board and Chief Executive Officer, ISIS Pharmaceuticals, Inc.
• Adjunct Professor of Pharmacology

TEL: 760-603-2301

FAX: 760-931-0265

Key Words: Antisense Oligonucleotides

Dr. Crooke is the Founder, Chairman and CEO and Lead Scientist at ISIS Pharmaceuticals. ISIS is a leader in the development of an exciting new class of human therapeutic compounds. These new compounds are based on oligonucleotides and related molecules and can be used to target diseases and health conditions not addressable by conventional therapeutic approaches. Since its founding in 1989, ISIS has advanced one antisense drug, Vitravene face="Symbol">Ô , to the market, six others to advanced clinical trials and numerous additional drugs into development.

Drug discovery at ISIS exploits two fundamental technologies. The company’s major focus is on antisense technology. Drugs based on the antisense mechanism can prevent cells in the body from producing disease-causing proteins and have the potential to be more specific (and less toxic) than compounds working through more conventional mechanisms. This technology also provides a rapid efficient means of genomic target validation.

The second technology is the mirror image of antisense. It focuses on the discovery of molecules that bind to structured sites in RNA. To do this, proprietary and highly innovative mass spectroscopic methods are required.

In 12 years ISIS has filed more than 1500 basic patents and has had nearly 800 issued.

Lima, W.F., Venkatraman, M., Crooke, S.T. The influence of antisense oligonucleotide-induced RNA structure on E. coli RNase H1 activity. J. Biol. Chem., 272(29):18199 (1997).

Lima, W.F., Crooke, S.T. Cleavage of single-strand RNA adjacent to RNA-DNA duplex regions by Escherichia coli RNase H1. J. Biol. *Chem., 272(44):27513-27516 (1997).

Wu, H., MacLeod, R., Lima, W.F., Crooke, S.T. Identification and partial purification of human double-strand RNase activity: a novel terminating mechanism for oligoribonucleotide antisense drugs. J. Biol. Chem., 273(5):2532-2542 (1998).

Graham, M.J., Crooke, S.T., Monteith, D.K., Cooper, S.R., Lemonidis, K.M., Stecker, K.K., Martin, M.J., Crooke, R.M. In vivo distribution and metabolism of a phosphorothioate oligonucleotide within rat liver after intravenous administration. J. Pharmacol. Exp. Ther., 286(1):447-458 (1998).

Crooke, S.T. (ed.) Antisense Research and Application. Handbook of Experimental Pharmacology Springer-Verlag, Berlin Heidelberg (1998).

Lima, W.F. and Crooke, S.T. Highly efficient endonucleolytic cleavage of RNA by a Cys₂His₂Zinc finger peptide. Proc. Natl. Acad. Sci., 96(18):10010-10015 (1999).

Griffey, R.H., Hofstadler, S.A., Sannes Lowery, K.A., Ecker, D.J., Crooke, S.T. Determinants of Aminoglycoside binding specificity for RNA using mass spectrometry. Proc. Natl. Acad. Sci., 96:10129-10133 (1999).

Wu, H., Lima, W.F., and Crooke, S.T. Properties of cloned and expressed Human RNase H. J. Biol. Chem., 274(40):28270-28278 (1999).