We propose to conduct a clinical study of an in vitro diagnostic system capable of detecting mutations in the gene related to cystic fibrosis (CFTR). The system consists of the cystic fibrosis DNA-based assay and supporting instrumentation. The assay was developed in the recently completed Phase II of SBIR grant number 2 R44 HL074607. The assay has extended mutation detection for two domestic ethnic groups, non- Caucasian Hispanics and African Americans, compared with the standard assay based on the 25-mutation panel recommended by American College of Medical Genetics. The assay also improves the coverage for Caucasians. The instrument is a bench-top flow fluorimeter capable of multiplexed analysis of the chips implemented in the assay. The goals of the project include: (1) performing developmental activities for each component of the system (microtransponders, flow reader and assays), (2) characterizing the system performance, (3) manufacturing the components for clinical trials, (4) conducting appropriate pre-clinical and clinical studies, and (5) preparing and submitting an abbreviated 510(k) to the FDA. The assay detects 50 CF mutations and is implemented on small electronic chips, called microtransponders. Each microtransponder is composed of photocells, antenna and memory to store information that identifies the sequence of the DNA probes attached to the microtransponder surface. In the assay, labeled target DNA binds to DNA probes and is visualized with a fluorescent staining reagent. The fluorescence intensity of the microtransponder surface is quantified in a flow-based instrument, which also reads the ID of the chip. The chips, as well as the instrumentation to read the chips, have been built by PharmaSeq.
The benefits of the program include improved detection of disease-related mutations, leading to better health care for cystic fibrosis-affected individuals, and extending clinical understanding of the genetic basis of cystic fibrosis. As an additional significant benefit, the instrumentation and the assay system will be made available for new genetic tests.
