Nucleic Acids with Novel Structures and Functions

描述(申请人提供)：这项建议汇集了实验室中以核酸结构、功能和操纵为中心的一些努力。所有这些计划都集中在通过合理的设计和分子进化相结合的方式来制造具有新奇性质的核酸和核酸络合物。特别是，我们正在尝试设计和表征具有基于金属络合的改变的碱基配对相互作用的新型DNA。最终，我们希望能够用酶法合成这种对，用于信息存储和具有新功能的核酸的体外进化。在更高的结构水平上，我们将尝试产生环状、折叠的RNA，这些RNA能够充当病毒-具有感染性，可以在体内复制，并可以调节细胞功能。这些分子将在基于细胞的功能基因组学以及可能的治疗应用中找到应用。最后，在选择性蛋白质-核酸复合体的水平上，我们试图产生一系列序列特异的重组酶，这些重组酶可用于克隆实验、细胞遗传干扰/插入实验，或者可能用于转基因动物实验。除了上述应用外，这些实验可能会为核酸的结构、功能和识别提供新的见解。

DESCRIPTION (provided by applicant): This proposal brings together a number of efforts in the lab centered on nucleic acid structure, function and manipulation. All these projects are focused on generating nucleic acids and nucleic acid complexes with novel properties by a combination of rational design and molecular evolution. In particular we are attempting to design and characterize novel DNAs with altered base-pairing interactions based on metal complexation. Ultimately, our hope is to be able to enzymatically synthesize such pairs to use in applications for information storage and the in vitro evolution of nucleic acids with novel functions. At a higher level of structure, we will attempt to generate circular, folded RNAs that are capable as acting as viruses- are infective, can be replicated in vivo, and can modulate cellular function. Such molecules would find applications in cell-based functional genomics and possibly therapeutic applications. Finally, at the level of selective protein-nucleic acid complexes, we are attempting to generate a series of sequence specific recombinases that can be used for cloning experiments, in cellular genetic disruption/insertion experiments, or possibly transgenic animal experiments. In addition to the applications described above, these experiments will likely provide new insights into nucleic acid structure, function and recognition.