SYSTEM FOR LARGE SCALE SYNTHESIS OF ANTISENSE OLIGOS

描述（改编自申请人摘要）：拟开发 用于大规模合成寡核苷酸的自动化系统 包括反义寡核苷酸。 用于寡聚物合成的方法具有 已开发用于小型塔或流化床，每个系列 添加一个寡核苷酸所需的反应物， 一段时间。 步骤之间的彻底清洗是必不可少的。 如果 反应体积将从目前的水平（从微升 和毫升），需要快速改变床体积的方法， 用于保持试剂之间的界面清晰，用于最小化异常 流量，用于减少每单位寡核苷酸所需的试剂体积 合成，并有效地阀的所有试剂与可忽略不计的死亡 音量. 为了避免试剂交叉污染一种新型的计算机- 还需要一个受控的零滞留阀， 多个（超过20个）不同的流体管线连接在任何 一条进口线。 解决放大问题所需的基本原则 从理论上解决了问题，并建造了合成釜。 本建议书旨在完成阀门系统， 反应容器，并用于评价整个系统中的流动，所有这些都在 一阶段

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.