Aptamer Development for Cancer Diagnosis and Management

用于癌症诊断和管理的适体开发

• 批准号: 6785751
• 负责人: JOSEPH S HEILIG
• 金额: $ 9.99万
• 依托单位: SOMALOGIC, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-19 至 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6785751
• 关键词: artificial intelligence; bioengineering /biomedical engineering; bioinformatics; biomarker; chemical binding; chemical synthesis; computational biology; computer program /software; early diagnosis; endopeptidases; enzyme complex; enzyme inhibitors; mathematics; microarray technology; molecular oncology; neoplasm /cancer diagnosis; oligonucleotides; proteomics; technology /technique development

DESCRIPTION (provided by applicant): Early diagnosis of disease allows for more effective therapy and better clinical outcomes. In cancer, extensive effort has gone toward development of screening and diagnostic techniques for early detection of disease. Despite this effort, the probability of single-analyte assays providing the "silver bullet" to address these problems for any specific tumor is vanishingly small. A more comprehensive approach that is more likely to succeed is the development of an integrated molecular diagnostic system using multiplexed assays of cancer-related biomarkers coupled with data analysis using bioinformatics-based algorithms. The development of multiplexed assays to improve quality of patient life is a major goal of SomaLogic. SomaLogic's proprietary nucleic-acid based capture agents, photoaptamers, yield quantitative analysis of proteins found in complex biological samples. Using data generated with this assay platform, we expect to develop predictive biomedical algorithms for the diagnosis and management of a variety of diseases, including cancer. The specific objective of this Phase I proposal is to develop an initial set of photoaptamers targeted to proteins and/or protein complexes that have been associated with a wide variety of solid tumors, i.e., proteinases, proteinase inhibitors, and proteinase-inhibitor complexes, which can then be used to screen clinical samples from patients with a variety of solid tumor types and stages of disease. The specific aims of the proposed research are to: 1) develop a set of well-defined photoaptamers specific for 20 proteinases, antiproteinases and proteinase-antiproteinase complexes that are believed to be associated with invasion and metastasis of solid tumors; 2) develop a photoaptamer microarray assay ("proteomics chip") for the measurement of at least 20 cognate proteins or protein complexes in serum or plasma; and 3) evaluate the ranges for these proteins or protein complexes in serum and plasma obtained from normal subjects. The overall objective of our research efforts in cancer is to develop CLIA-compatible assays and algorithm-based analysis systems for the monitoring of patients at risk for or diagnosed with various malignancies using aptamers directed against proteins that are either generally associated (proteinases, antiproteinases, adhesion molecules chemokines and/or chemokine receptors) or specifically associated (known cell markers, tissue specific proteins, transcriptional regulators, etc.) with solid tumors.

描述（由申请人提供）：疾病的早期诊断可以进行更有效的治疗和更好的临床结果。 在癌症中，为了开发筛查和诊断技术以促进疾病的早期发现。尽管做出了这种努力，但单分析物测定的可能性提供了“银弹”来解决这些特定肿瘤的这些问题的可能性很小。更有可能成功的一种更全面的方法是使用与癌症相关的生物标志物的多重测定以及使用基于生物信息学的算法的数据分析的多重测定法开发了综合分子诊断系统。多路复用测定的开发以提高患者寿命的质量是索拉的主要目标。基于核酸的专有捕获剂，光照相剂，对复杂生物样品中发现的蛋白质的定量分析。使用此测定平台生成的数据，我们希望开发预测性生物医学算法，以诊断和管理各种疾病，包括癌症。 该阶段提案的具体目的是开发针对蛋白质和/或蛋白质复合物的初始光照射器，这些光致蛋白质和/或蛋白质复合物与多种固体瘤，即蛋白酶，蛋白酶抑制剂和蛋白酶抑制剂络合物有关，然后可以将其用于从各种固体肿瘤类型和疾病的患者中筛查临床样本。拟议的研究的具体目的是：1）开发一组针对20种蛋白酶，抗蛋白酶酶和蛋白酶 - 抗激酶蛋白酶复合物特异性的光照相蛋白，这些光蛋白酶酶和蛋白酶 - 抗激酶酶络合物被认为与固体肿瘤的浸润和转移有关； 2）开发一种光照射微阵列测定（“蛋白质组学芯片”），以测量血清或血浆中至少20种同源蛋白或蛋白质复合物； 3）评估从正常受试者获得的血清和血浆中这些蛋白质或蛋白质复合物的范围。 我们在癌症研究工作的总体目标是开发与CLIA兼容的测定和基于算法的分析系统，以监测针对蛋白质的适体（通常相关的蛋白酶）（蛋白酶，抗蛋白酶，抗蛋白酶，粘附分子）趋化因子和/或特异性的细胞级别的细胞（已知的蛋白酶）（已知的蛋白酶）（已知的蛋白酶），或者是相关的蛋白质（抗蛋白酶），以监测患有或诊断出患有各种恶性肿瘤的患者，或者是相关的。等）有实体瘤。