SYSTEM FOR LARGE SCALE SYNTHESIS OF ANTISENSE OLIGOS

大规模合成反义寡核苷酸的系统

• 批准号: 3498780
• 负责人: NORMAN G ANDERSON
• 金额: $ 5万
• 依托单位: LARGE SCALE BIOLOGY CORPORATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1992-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3498780
• 关键词: antisense nucleic acid; biomedical automation; biomedical equipment development; bioreactors; centrifugation; computers; fluid flow; nucleic acid chemical synthesis; oligonucleotides; synthetic nucleic acid

DESCRIPTION (Adapted from applicant's abstract):It is proposed to develop an automatic system for the large-scale synthesis of oligonucleotides including antisense oligonucleotides. Methods for oligo synthesis have been developed for small columns or fluidized beds, with each of the series of reactants necessary to add one oligonucleotide present only for short periods of time. Complete washing between steps is essential. If the reaction volume is to be scaled up from present levels (from microliters and milliliters), methods are required for rapidly changing bed volumes, for keeping interfaces between reagents sharp, for minimizing anomalous flow, for reducing the volume of reagents required per unit oligo synthesized, and for effective valving of all reagents with negligible dead volume. To avoid reagent cross-contamination a new type of computer- controlled zero-hold-up valve is also required which will allow larger numbers (more than twenty) of different fluid lines to be connected in any order to one inlet line. The basic principles required to solve scale-up problems have been worked out in theory, and the synthesis vessel built. This proposal is for completion of the valving system, for modifications of the reaction vessel, and for evaluation of flow in the total system, all in Phase I.

描述(改编自申请人的摘要)：建议开发 一种大规模合成寡核苷酸的自动化系统 包括反义寡核苷酸。寡聚合成的方法有 是为小型塔或沸腾床开发的，每一系列 添加一种寡核苷酸所需的反应物仅短暂存在 一段时间。两步之间的彻底洗涤是必不可少的。如果 反应体积将从目前的水平(微升)扩大 和毫升)，需要用于快速改变床体积的方法， 保持试剂之间的界面清晰，最大限度地减少异常 流程，用于减少每单位寡聚所需试剂的体积 合成的，用于所有试剂的有效阀门，而死亡可以忽略不计 音量。为了避免试剂交叉污染，一种新型的计算机- 还需要控制零保持阀，这将允许更大的 要连接的不同流体管路的数量(多于20条) 订购到一条进口管路。解决规模扩大所需的基本原则 从理论上解决了问题，并建造了合成罐。 本提案是为了完成阀门系统，以便对 反应容器，以及用于评估整个系统中的流动，全部在 第一阶段。