An Expanded Genetic Information System

描述(由申请人提供)：DNA字母表不限于 四个标准核苷酸。相反，形成6个碱基对的12个碱基 通过相互排斥的氢键模式连接在 沃森-克里克碱基对的几何结构。这些形成了一种扩展的基因 信息系统(Aegis)--一种新的基于规则的分子识别系统 它携带蛋白质功能，可以以组合形式制备，并且 可以像复制核酸一样被复制。鉴于对此的丰富理解 系统经过十年在本纳实验室的研究，宙斯盾是一个 技术转让机会。在第一阶段的研究中，一套全面的 实验验证了宙斯盾能够提供一组正交性， 无交叉反应标签对支持高度多路传输(100或更多)很有用 DNA诊断系统。这些研究包括对解决方案和 固相，使用支持多路传输的Luminex仪器，以及 聚合酶。在第二阶段，我们将制备1000个独立结合的类DNA 标签，进一步开发工具来支持个别患者的基因分型，以及 选择同时包含官能化核苷酸和 将宙斯盾组分转化为寡核苷酸。 建议的商业应用： 支持“基于规则的分子识别”的化学系统具有广泛的商业适用性，包括未来的“蓝天”(例如纳米技术和分子计算)。更直接的是，这里的宙斯盾系统支持商业诊断系统，并在第一阶段导致了一种检测单核苷酸多态(SNPs)的检测方法。这样的分析预示着预测性医学和个性化护理领域的一场革命，具有潜在的市场价值。

DESCRIPTION (provided by applicant): The DNA alphabet is not limited to the four standard nucleotides. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick base pair. These form An Expanded Genetic Information System (Aegis), a new, "rule based" molecular recognition system that carries protein functionality, can be prepared in combinatorial form, and can be copied much like nucleic acids. Given the rich understanding of this system after a decade of research in the Benner laboratory, Aegis is a technology transfer opportunity. In the Phase I study, a comprehensive set of experiments validated the ability of Aegis to provide a set of orthogonal, non-cross reacting tags useful to support highly multiplexed (100 or more analytes) DNA diagnostics systems. These included studies in both solution and solid phase, with the Luminex instruments that support multiplexing, and with polymerases. In Phase II, we will prepare 1000 independently binding DNA-like tags, further develop tools to support genotyping of individual patients, and select for polymerases that incorporate both functionalized nucleotides and Aegis components into oligonucleotides. PROPOSED COMMERCIAL APPLICATION: Chemical systems that support "rule based molecular recognition" have wide commercial applicability, including in come "blue skies" (nanotechnology and molecular computing, for example). More immediately, the Aegis system here is supporting a commercial diagnostics system, and has led in the Phase I period to an assay that detects single nucleotide polymorphisms (SNPs). Such assays promise a revolution in predictive medicine and personalized care, with potential market value.