NUCLEIC ACID TRIGGERED DRUG & PROBE RELEASE

核酸触发药物

• 批准号: 8361329
• 负责人: JOHN-STEPHEN Adolfino TAYLOR
• 金额: $ 0.29万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361329
• 关键词: Base Sequence; Biological; Cell Death; Cells; Cessation of life; Cytotoxic agent; DNA Sequence; Disease; Drug Formulations; Funding; Genetic; Grant; Mass Spectrum Analysis; Messenger RNA; National Center for Research Resources; Nucleic Acids; Nucleic acid sequencing; Pharmaceutical Preparations; Principal Investigator; Prodrugs; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; biomedical resource; catalyst; chemotherapeutic agent; chemotherapy; cost; design

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该项目的目的是开发一种新的和一般的方法来设计和合成易于编程的，疾病特异性的化学治疗剂，并直接利用遗传信息来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序列来指导能够将亲毒品转化为活性药物的激活剂和激活剂的关联。 在这种方法中，核酸不被用作靶标，而是用作触发因素，因此不取决于疾病特异性核酸序列的生物学活性，仅取决于其独特性和可及性。 我们正在研究这种新概念对化学疗法的一种表述的可行性，在该化学疗法中，亲药成分由与PNA段相连的药物组成，该药物与疾病特异性mRNA的一部分互补，并且激活成分由A组成。催化剂附着在mRNA的相邻截面上的PNA段上。 只有在患病的细胞中，特定的mRNA才会导致两个成分相关，从而导致促毒物转化为细胞毒性药物和细胞死亡。