SBIR Phase II: New Labeling Reagents for Genetic Analysis

这个小企业创新研究二期项目旨在开发新的、灵敏、准确和可靠的检测方法，用于测量从活细胞中分离的基因组DNA或RNA样本。该项目的智力价值在于开发新的检测方法，这些方法对于提高基因活性的高通量基因组微阵列分析至关重要。当前微阵列和基因组分析技术的问题，包括杂交扰动，使用昂贵的标记核苷酸和序列依赖的慢酶标记方法，使用直接标记方法解决。这些新系统将提供所需的检测工具，以推进基因组分析在有前途的制药、研究和诊断方面的应用，以确定疾病或治疗过程中的基因表达模式。Marker Gene Technologies, Inc.已经通过制备新的超灵敏荧光标记试剂和开发直接标记从活细胞中分离的DNA或RNA样品的方案，建立了这些检测方法的可行性。这些试剂能够高效、灵敏地标记寡核苷酸，用于高通量微阵列分析。在II期中，这些系统将通过进一步分析荧光标记方法和表征其监测药物或其他生物活性化合物应用时基因表达变化的能力来验证，或者以细胞特异性的方式响应细胞功能或疾病的生物变化。该项目的更广泛影响包括开发和商业化快速筛选基因组表达模式的新方法，以响应正常细胞和组织以及疾病、细菌或病毒感染中的特定药物应用。这些方法通过使用更快、更准确和更具成本效益的直接标记方法，对现有技术进行了重大改进。这些系统将被销售给制药和诊断行业，用于通过比较细胞基因组分析进行药物疗效的高通量临床前筛选。此外，与工业和研究伙伴的现有合作确保了该技术的快速商业发展。这些技术的结合将提高美国在新兴的基因组分析领域和药物治疗药物开发方面的竞争力，并基于所开发的产品和系统创造更多的就业机会。

This Small Business Innovation Research Phase II project aims to develop new, sensitive, accurate, and reliable detection methods for measuring genomic DNA or RNA samples isolated from living cells. The intellectual merit of this project lies in the development of new detection methods that are essential for improving high-throughput genomic microarray analyses of gene activity. Problems with current microarray and genomic analysis techniques, including hybridization perturbation, slow enzymatic labeling methods using expensive labeled nucleotides and sequence dependence, are solved using a direct labeling approach. These new systems will provide the detection tools needed to advance the promising pharmaceutical, research and diagnostic uses of genomic analysis to determine the pattern of gene expression in disease or upon therapeutic treatment. Marker Gene Technologies, Inc. has established the feasibility of these detection methods by preparing new ultrasensitive fluorescent labeling reagents and developing protocols for directly labeling DNA or RNA samples isolated from live cells. These reagents are able to efficiently and sensitively label oligonucleotides for high-throughput microarray analysis. In Phase II these systems will be validated by further analysis of the fluorescent labeling methods and characterization of their ability to monitor changes in gene expression upon application of drugs or other bioactive compounds or in response to biological changes in cell function or disease, in a cell-specific manner. The broader impacts of this project include development and commercialization of new methods for rapid screening of genomic expression patterns in response to specific drug application in normal cells and tissues as well as in disease, bacterial or viral infections. These methods are a significant improvement over existing technologies by using a direct labeling approach that is quicker, more accurate and more cost-effective. These systems will be marketed to the pharmaceutical and diagnostics industries for high-throughput pre-clinical screening of drug efficacy by comparative cellular genomic analysis. In addition, existing collaborations with industrial and research partners assure quick commercial development of the technology. The combined techniques will improve U.S. competitiveness in the burgeoning genomic analysis field as well as in pharmaceutical therapeutic drug development and lead to further job creation based on both the products and systems developed.