Development of Liposome Complexed RNA Quality Controls

描述（由申请人提供）：新型分子实验室测试的爆炸式增长显著改善了白血病的诊断和管理，但用于测试验证的稳定对照的可再生供应问题尚未解决。目前使用细胞系或患者标本进行质量保证的范例是不令人满意的，因为材料不稳定，具有潜在传染性，供应有限，并且不能通过常规测试提取进行处理。病人保密是有问题的，每个标本只有一种基因型，因此控制多重测试，包括基因芯片，非常昂贵。II期将生产合成的、稳定的、非传染性的、多分析物对照物，以保证基于分子的白血病检测的质量。我们的新方法的可行性通过I期生产稳定的阳离子脂质体复合物RNA得到了证明，该RNA在BCR-ABL临床试验中可用作对照。全面的白血病控制集的二期生产开始于创建另外七个包含白血病基因片段的克隆库。RNA将在体外产生，并用I期专有技术生成的脂质体复合物稳定。参考基因片段将被纳入，以使用于指导治疗的最小残留疾病定量测试有用的对照。拟议的项目为支持和实施白血病的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.