Low-cost, Sequence-based Cancer Pharmacogenetics

Period of Performance: 06/19/2000 - 02/28/2001

$448K

Phase 2 SBIR

Recipient Firm

Oscient Pharmaceuticals Corporation
Waltham, MA 02453
Principal Investigator

Abstract

The goal of this project is to develop new techniques for Ultra High Throughput Sequencing to enable rapid, low cost pharmacogenetic analysis of genes involved in cancer susceptibility, progression, and treatment. Overall, a 5-fold reduction in-costs will be achieved compared to "l/4x" ABI sequencing reactions. Part of this cost reduction will be achieved through efficient sample handling of small volume reactions, the remainder will be achieved through reduction in labor and plastic consumables associated with sample preparation and processing. The core of the sample handling system will be a 96-channel device for capillary-based aspiration and delivery that will utilize standard micro-well plates as reagent sources. Once the samples have been processed, they will be returned to micro-well plates for loading onto slab-gel or capillary electrophoresis sequencing instruments. The sample-handling device will have integrated pipetting, thermocycling and purification capabilities. Removal of undesirable contaminants from the thermocycling reaction will be accomplished by means of a novel microdialysis procedure. "Proof of principle" testing of capillary-based thermocycling, and the discovery, testing and initial optimization of the purification technology was performed under Phase I of this study. In Phase II, a small footprint, modular sample processing system will be built, and direct sequencing assays tests for five specific genes involved in cancer susceptibility and drug response will be implemented and executed on a panel of 360 human DNA samples of globally diverse ethnic origin. PROPOSED COMMERCIAL APPLICATIONS: GTC is developing sequence-based pharmacogenetics capabilities to provide accurate, cost effective tests for genes involved in drug metabolism and oncology. The Company is pursuing business opportunities with pharmaceutical companies, linking information on sequence variation with disease states and drug response phenotypes to stratify patient populations for lead optimization and clinical trials.