Nucleic Acids with Novel Structures and Functions

描述（由申请人提供）：本提案汇集了实验室以核酸结构，功能和操作为中心的许多努力。所有这些项目的重点是通过合理设计和分子进化相结合，产生具有新特性的核酸和核酸复合物。特别是，我们正试图设计和表征基于金属络合改变碱基配对相互作用的新型dna。最终，我们的希望是能够酶促合成这些对，用于信息存储和具有新功能的核酸的体外进化。在更高层次的结构上，我们将尝试产生环状的折叠rna，它们能够像病毒一样起作用——具有传染性，可以在体内复制，并且可以调节细胞功能。这些分子将应用于基于细胞的功能基因组学，并可能用于治疗。最后，在选择性蛋白-核酸复合物的水平上，我们正试图产生一系列序列特异性重组酶，这些重组酶可用于克隆实验、细胞遗传破坏/插入实验或可能的转基因动物实验。除了上述应用之外，这些实验可能会对核酸的结构、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.