Rigel technology enables expression of peptide libraries inside mammalian cells

Combinatorial biology technology could become important drug discovery tool

Research published in the January 2001 issue of Nature Genetics shows that Rigel Pharmaceuticals Inc.'s (South San Francisco, CA) combinatorial biology technology can be useful in rapidly and efficiently identifying novel, functional drug targets in disease signaling pathways.

According to the report, Rigel's technology, licensed from the laboratory of Garry P. Nolan at Stanford University, enables the expression of peptide libraries inside mammalian cells, giving rise to a new way to approach functional genomics. Historically, researchers have experienced technical difficulty achieving intracellular expression of large numbers of functionally active peptides and proteins, which inhibited their ability to precisely identify targets inside a cell that could reverse a disease process. Rigel's technology offers researchers a simple yet powerful, broadly applicable method to decipher the complex signaling pathways inside a cell.

"The ability to rapidly and precisely identify functional drug targets and understand how they impact complex signaling pathways is considered a key challenge in drug discovery in the post-genomic era," Donald Payan, Rigel's executive vice president and chief scientific officer, said in a company release.

"Our combinatorial biology technology, which offers the first demonstration of a practical way to get at large-scale functional genomics in mammalian systems, provides a functional means to identify potential drug-target candidates as well as a biological understanding of human cellular disease mechanisms," Payan, an author on the Nature Genetics study, added. "Moreover, our proprietary technology is broadly applicable to a wide range of biological questions and their related disease states, making Rigel an attractive partner to pharmaceutical companies that need to fill their drug pipelines."

The Nature Genetics study and accompanying editorial reports Rigel's success in applying its combinatorial biology technology to the emerging clinical problem of resistance to the anti-cancer drug, Taxol, to demonstrate proof-of-principle of this novel approach to functional genomics. The researchers used retroviruses to deliver a different peptide inside each of millions of mammalian tumor cells to see which tumor cells could survive when treated with the cancer-killing agent. Using Rigel's proprietary functional assays that are designed to identify the peptides that change the cell's biological outcome in the desired way (i.e., those tumor cells that survive in the presence of Taxol), the researchers identified seven peptides that allowed for increased Taxol resistance, one of which consistently had the highest survival rate and was linked to upregulation of the gene ABCB1 (also known as MDR1 for multiple drug resistance). The technology also allows for the isolation and recovery of the target to which the peptide bound, and enables researchers to determine the mechanism by which the peptide exerts its effect.

Rigel uses combinatorial biology technology to discover novel drug targets.

For more information: Rigel Pharmaceuticals Inc., 240 E. Grand Ave., South San Francisco, CA 94080. Tel: 650-624-1100. Fax: 650-624-1101.

With contributions from Jim Pomager
Assistant Editor, Bioresearch Online
Source: Rigel Pharmaceuticals Inc.