NUCLEIC ACID TRIGGERED DRUG & PROBE RELEASE

核酸触发药物

• 批准号: 7721426
• 负责人: JOHN-STEPHEN Adolfino TAYLOR
• 金额: $ 0.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721426
• 关键词: Base Sequence; Biological; Cell Death; Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic agent; DNA Sequence; Disease; Drug Formulations; Funding; Genetic; Grant; Institution; Messenger RNA; Nucleic Acids; Nucleic acid sequencing; Peptide Nucleic Acids; Pharmaceutical Preparations; Prodrugs; Research; Research Personnel; Resources; Source; United States National Institutes of Health; catalyst; chemotherapeutic agent; chemotherapy; concept; design

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of this project is to develop a new and general approach to the design and synthesis of easily programmable, disease-specific chemotherapeutic agents and probes that make direct use of genetic information to trigger the death of a diseased cell. The idea is to make use of a disease-specific mRNA or DNA sequence to direct the association of a pro-drug and an activator capable of converting the pro-drug to an active drug. In this approach the nucleic acid is used not as a target, but as a trigger, and thus does not depend on the biological activity of the disease-specific nucleic acid sequence, only on its uniqueness and accessibility. We are investigating the feasibility of one formulation of this new concept to chemotherapy in which the pro-drug component consists of a drug attached to a segment of PNA that is complementary to one section of a disease specific mRNA, and the activating component consists of a catalyst attached to a segment of PNA that i s c omplementary to the adjoining section of the mRNA. Only in a diseased cell can the disease specific mRNA cause the two components to associate which then results in the conversion of the pro-drug to a cytotoxic drug and death of the cell.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目的是开发一种新的通用方法来设计和合成易于编程的、疾病特异性的化疗药物和探针，这些药物和探针直接利用遗传信息来触发疾病细胞的死亡。这个想法是利用疾病特异性的mRNA或DNA序列来指导前药物和能够将前药物转化为活性药物的激活剂之间的关联。在这种方法中，核酸不被用作目标，而是被用作触发物，因此不依赖于特定于疾病的核酸序列的生物活性，而仅取决于其唯一性和可及性。我们正在研究将这一新概念用于化疗的一种配方的可行性，其中前药物成分由连接到与疾病特异性基因片段互补的一段PNA上的药物组成，而激活成分由连接到一段PNA上的催化剂组成，S补充相邻的一段基因。只有在患病的细胞中，疾病特异性信使核糖核酸才能使这两种成分结合在一起，从而导致前药物转化为细胞毒性药物，并导致细胞死亡。