DESIGN AND SELECTION OF RIBOZYMES FOR HIV THERAPY

描述(改编自调查人员摘要)：本报告的目的 建议是开发催化RNA或核酶用于治疗的用途。 锤头的研究工作将继续进行，锤头是一种具有良好特征的RNA切割 试剂，重点是了解为什么嵌入的靶的切割 大的RNA通常比短的寡聚体慢得多。此外, 给出了获得靶元速率常数的实验方法。 为了更好地在细胞内结合和切割锤头 相关的体外和体内实验。最后，最近的发现 交联型锤头是一种有效的rna连接酶将会被研究。 目的是将其用作RNA修复试剂。为了扩大规模 可用于治疗的核酶谱系，两个体外实验 提出了旨在识别小说的选择策略 作用于蛋白质的核酶。一个选择将搜索一个 一种是脱磷酸酶，另一种是肽酶。

DESCRIPTION (Adapted from the Investigator's Abstract): The aims of this proposal are to develop the use of catalytic RNAs or ribozymes for therapy. Work will continue on the hammerhead, a well-characterized RNA cleavage reagent, with a focus on understanding why cleavage of a target embedded in a large RNA is often much slower than short oligomers. In addition, experiments are proposed to obtain the elemental rate constants of target binding and cleavage for a hammerhead inside cells in order to better correlate in vitro and in vivo experiments. Finally, the recent discovery that a crosslinked hammerhead is an effective RNA ligase will be studied with the aim of using it as an RNA repair reagent. In an attempt to expand the repertoire of ribozymes that could be used in therapy, two in vitro selection strategies are proposed that are intended to identify novel ribozymes that act on proteins. One selection will search for a dephosphorylase, the other a peptidase.