SBIR-STTR Award

The overall goal of this proposal is to develop and implement an integrated suite of technologies for enabling microarray-based diagnostic assays and the cGMP manufacturing processes and procedures necessary to manufacture these products. Microarrays have found widespread use in biology and medicine as important tools for evaluating gene expression and genomics. Microarrays offer tremendous promise to meet the needs of complex analyte detection for improved patient care in situations in which clinical decisions must be informed by classifiers based on inputs from large sets of features. Adoption of arrays for clinical diagnostics is inevitable. As an example, Agendia BV has received FDA approval for the first array-based IVDMIA diagnostic assay (Mammaprint) for evaluating the prognosis of patients with breast cancer. This assay is based on measuring the expression of a set of 70 genes which is normalized to the expression of hundreds of additional features present on the microarray as well as dozens of control features. This level of multiplexing is not currently feasible using any other platform for measuring gene expression. The implementation of diagnostic microarrays on a wide basis will require the development and manufacture of enabling technologies that are robust and reproducible and can be performed reliably and efficiently in the clinical diagnostic laboratory setting. Development and manufacture of these products using rigorous design controls and manufacturing processes are essential to achieving inter-laboratory consistency and obtaining regulatory approval and reimbursement. Asuragen was spun out of Ambion to commercialize diagnostic applications of RNA-related research products technologies. Asuragen scientists played key roles in the development of Ambion's MessageAmp and MessageAmp II RNA market leading amplification products. Asuragen's cGMP manufacturing and development capabilities, rights to Ambion IP for clinical applications, and Asuragen Services' state of the art gene expression profiling expertise will help drive the successful development of RNA amplification products for rapid integration into clinical diagnostics. In phase I we will develop a streamlined RNA amplification product suitable for implementation into clinical diagnostic laboratories. This product will provide representative RNA amplification suitable for use with all major microarray platforms. The specific aims are: 1) Develop and optimize a streamlined workflow for linear amplification of RNA for diagnostic microarray applications; and 2) Demonstrate the reliability and reproducibility of the streamlined amplification process for microarray applications. In phase II we will develop streamlined quality control and material qualification assays, and integrate the amplification product with other enabling products including sample RNA preservation and process controls and standards. These products will benefit human health by accelerating adoption of diagnostic microarrays.

Public Health Relevance:
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The overall goal of this proposal is to develop and implement an integrated suite of technologies for enabling microarray-based diagnostic assays and the cGMP manufacturing processes and procedures necessary to manufacture these products. Microarrays have found widespread use in biology and medicine as important tools for evaluating gene expression and genomics. Using these tools, clinical researchers are driving the characterization of the molecular signatures of disease as they relate to both prognosis and therapy. By resolving the detection of complex analyte mixtures, microarray technology offers tremendous promise to improve patient care in situations in which clinical decisions must be informed by classifiers based on inputs from large sets of features. Broader implementation of diagnostic microarrays will require the development and manufacture of enabling technologies that are robust and reproducible and can be performed reliably and efficiently in the clinical diagnostic laboratory setting. Rigorous control of design and manufacturing processes of these products is essential to achieving inter-lot, inter-laboratory consistency and obtaining regulatory approval and reimbursement. The solutions to these issues should enable much more widespread implementation of diagnostic microarrays and the corresponding advances in human healthcare that are promised by molecular diagnostics. Phase I activities have resulted in the development of a cGMP manufactured, single-tube, streamlined amplification format that shows excellent correlation with industry- standard research-grade amplification reagents. This Phase II application outlines the steps we will take to expand features of this product to be the most comprehensive amplification format. The investigations in this grant will be directed toward the development of a thorough set of quality control features and assays that will give information suitability of the reagents for microarray outcomes.

Public Health Relevance:
As understanding of human disease progresses and new methods for high throughput analyses continue to be developed, molecular diagnostics testing is becoming more accurate but more complicated. Our investigations will provide quality and control tools to ensure that these diagnostic tests can be used in clinical laboratories.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
There Are No Thesaurus Terms On File For This Project.