Development of Liposome Complexed RNA Quality Controls

描述（由申请人提供）：新的分子实验室检测的激增显著改善了白血病的诊断和管理，但用于检测验证的稳定对照品的可再生供应问题尚未解决。目前使用细胞系或患者样本进行质量保证的范例并不令人满意，因为材料不稳定，具有潜在感染性，供应有限，并且无法通过常规试验浸提进行处理。病人的保密性是有问题的，每个标本只有一个基因型，从而使控制多重测试，包括基因芯片，过于昂贵。第二阶段将生产合成的、稳定的、非感染性的、多分析物对照品，用于分子基础白血病检测的质量保证。我们的新方法的可行性得到了证明，第一阶段生产的稳定，阳离子脂质体复合RNA，作为控制在BCR-ABL临床试验。第二阶段生产的一个全面的白血病控制集开始创建七个额外的克隆银行含有白血病基因片段。RNA将在体外产生，并使用I期专有技术产生的脂质体复合物进行稳定。将纳入参考基因片段，以提供可用于指导治疗的微小残留疾病定量检测的对照。拟议的项目为支持和实施白血病关键分子检测做出了重大贡献。

DESCRIPTION (provided by applicant): The explosion of new molecular laboratory tests has significantly improved diagnosis and management of leukemia, but the problem of a renewable supply of stable controls for test validation has not been resolved. The current paradigm of using cell lines or patient specimens for quality assurance is unsatisfactory because materials are unstable, potentially infectious, of limited supply, and cannot be processed through routine test extractions. Patient confidentiality is problematic and each specimen has only one genotype, thus making control of multiplex tests, including gene chips, prohibitively expensive. Phase II will produce synthetic, stable, non-infectious, multi-analyte controls for quality assurance of molecular-based leukemia tests. Feasibility of our novel approach was demonstrated by Phase I production of stable, cationic liposome-complexed RNA, useful as controls in BCR-ABL clinical tests. Phase II manufacture of a comprehensive Leukemia Control Set begins by creating seven additional clone banks containing leukemic gene segments. RNA will be produced in vitro and stabilized with liposome complexes generated by Phase I proprietary techniques. Reference gene segments will be incorporated to render controls useful for minimal residual disease quantification tests used to direct therapies. The proposed project makes a significant contribution to the support and implementation of critical molecular tests for leukemia.