NUCLEIC ACID TRIGGERED DRUG & PROBE RELEASE

核酸触发药物

• 批准号: 7953885
• 负责人: JOHN-STEPHEN Adolfino TAYLOR
• 金额: $ 0.51万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953885
• 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; Mass Spectrum Analysis; Messenger RNA; Nucleic Acids; Nucleic acid sequencing; Pharmaceutical Preparations; Prodrugs; Research; Research Personnel; Resources; Source; United States National Institutes of Health; biomedical resource; catalyst; chemotherapeutic agent; chemotherapy; 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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化疗剂和探针，直接利用遗传信息触发患病细胞的死亡。 这个想法是利用疾病特异性的 mRNA 或 DNA 序列来指导前药和能够将前药转化为活性药物的激活剂的结合。 在这种方法中，核酸不用作靶标，而是用作触发物，因此不依赖于疾病特异性核酸序列的生物活性，仅依赖于其独特性和可接近性。 我们正在研究这一化疗新概念的一种配方的可行性，其中前药成分由附着在 PNA 片段上的药物组成，该片段与疾病特异性 mRNA 的一个片段互补，而激活成分由催化剂附着在 PNA 的一段上，该段与 mRNA 的相邻部分互补。 只有在患病细胞中，疾病特异性 mRNA 才能导致两种成分结合，然后导致前药转化为细胞毒性药物并导致细胞死亡。