SBIR-STTR Award

Hyseq, in collaboration with the Malaria Initiative Program at Harvard University's School of Public Health, is seeking to determine the feasibility for developing a DNA chip as a diagnostic tool for malaria genotyping and polymorphism identification under a Phase I SBIR grant. Hyseq possesses DNA chip technology that has accurately tested polymorphisms in HIV and human DNA, and plans to apply this technology to malaria strains. Harvard's Malaria Initiative will supply genornic DNA samples of the most prevalent malaria strain, Plasmodzium falciparum, to Hyseq for the development of a DNA chip as a diagnostic tool for use in the field, research, and by clinicians in order to identify and characterize drug resistant stins of malaria and their mutations (e.g., resistance to cholorquine, fanzidar, etc). The aims of Phase I research are: l) to develop protocols and components for rapid diagnosis of drug resistant strains of P. falciparum using Hyseq's proprietary DNA chip technology, and 2) apply the developed chip to detect known mutations associated with the DHFR and pfindri drug-resistant genes and determine the efficacy and accuracy of the chips performance. The long term objective of the research and development is to develop an inexpensive DNA chip for rapid diagnosis and genotyping of drug-resistant malaria to optimize the best suited drug therapy. PROPOSED COMMERCIAL APPLICATION: A specially designed malaria DNA chip for rapid, inexpensive, and accurate diagnosis of multiple drug resistant strains to assist proper patient treatment in the field, clinics, and hospitals. In addition, the chip will greatly benefit research organiztions to monitor drug-resistant strains in populations, map evolvittg mutant strains during the course of infection, and discover of new mutations

Callida Genomics (a majority owned subsidiary of Hyseq Pharmaceuticals), in collaboration with the Malaria Initiative Program at Harvard University School of Public Health, is developing universal DNA arrays for discovery and genotyping of drug resistance mutations in the malaria parasite Plasmodium falciparum. The process is based on Callida's Sequencing by Hybridization technology which is capable of routine whole gene sequencing and universal multiplex genotyping. Three prototype products will be developed and used by both Harvard and Callida's laboratories to sequence and genotype several genes in approximately 150 malaria patient samples with precisely characterized drug resistance levels. The project involves sequencing a total of 2.3 MB of malaria parasite DNA in order to discover new drug resistant mutations with high predictive efficiency. The project's long term objective is to optimize therapy and disease management procedures by developing an inexpensive and accurate diagnostic chip-based kit. The kit is designed to detect in a single assay all known drug resistant mutations of P. falciparum including new mutations discovered during this project. This innovative and efficient universal system can be used in any laboratory for rapid DNA sequence analysis of any pathogen DNA for multiple research, diagnostic and biodefense applications.

Thesaurus Terms:
Plasmodium falciparum, drug resistance, genetic polymorphism, genotype, malaria, microarray technology, nucleic acid sequence, technology /technique development communicable disease diagnosis, diagnosis design /evaluation, dihydrofolate reductase, gene mutation, genetic strain