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Enzyme Bioreactor for Optimized Production of Modified Nucleic Acids

用于优化生产修饰核酸的酶生物反应器

基本信息

批准号：
8195405
负责人：
Peter B Allen
金额：
$ 5.13万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8195405
关键词：
Automation Biochemical Biochemical Reaction Biopolymers Bioreactors Biosensor Blood Chemical Industry Chemicals DNA Data Collection Development Environment Enzymes Evaluation Feedback Genetic Transcription Goals Immobilized Enzymes In Vitro Injection of therapeutic agent Investigation Laboratories Liquid substance Manuals Methods Microfluidics Monitor Nucleic Acids Oligonucleotides Organic Chemistry Pharmaceutical Preparations Play Polymerase Process Production Property Protocols documentation Pump RNA Reaction Resistance Robotics Role Small Interfering RNA Standard Preparations Structure Techniques Therapeutic Therapeutic Agents Translating analog aptamer base biological systems cancer cell chemical synthesis computerized tools design detector directed evolution drug candidate improved in vivo instrument macromolecule meetings nuclease operation programs public health relevance research clinical testing research study sensor skills small molecule tool

项目摘要

DESCRIPTION (provided by applicant): We will develop optimized methods for the enzymatic production of modified oligonucleotides which have strong advantages as therapeutic agents and biosensors. We will first implement a Sequential Injection Analysis (SIA) platform with continuous data collection to optimize biochemical protocols with large parameter spaces. We will use this platform to optimize conditions for in vitro transcription of 2'-O-methyl and 2'-fluoro RNA. We will also implement a continuous, continuous- or semi-continuous-flow bioreactor for in vitro production of modified RNA for use in ongoing projects including microfluidic cancer cell capture and in vivo evaluations of aptamer therapeutics. Microreactors of the type we will build have been demonstrated for controlled, efficient, scalable, synthetic organic chemistry. These same advantages make the strategy attractive for biochemical reactions. PUBLIC HEALTH RELEVANCE: Chemically modified DNA and RNA are more resistant to being destroyed by the environment in blood, and so they are preferred as tools to develop drugs or instruments used for clinical testing. Current methods for generating these valuable substances are very expensive and produce very little of the product, which limits their use. This project will develop an improved method to generate modified DNA and RNA which will allow wider use of these important chemical tools.

描述（由申请人提供）：我们将开发用于酶促生产修饰寡核苷酸的优化方法，其作为治疗剂和生物传感器具有强大的优势。我们将首先实施连续注射分析（SIA）平台，通过连续数据收集来优化具有大参数空间的生化方案。我们将使用该平台来优化 2'-O-甲基和 2'-氟 RNA 的体外转录条件。我们还将实施连续、连续或半连续流生物反应器，用于体外生产修饰的 RNA，用于正在进行的项目，包括微流体癌细胞捕获和适体疗法的体内评估。我们将建造的这种类型的微反应器已被证明可用于受控、高效、可扩展的合成有机化学。这些相同的优点使该策略对生化反应具有吸引力。公共卫生相关性：化学修饰的 DNA 和 RNA 更能抵抗血液中环境的破坏，因此它们是开发用于临床测试的药物或仪器的首选工具。目前生产这些有价值物质的方法非常昂贵，而且产量很少，这限制了它们的使用。该项目将开发一种改进的方法来生成修饰的 DNA 和 RNA，这将使这些重要的化学工具得到更广泛的使用。