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    • 2. 发明申请
    • NUCLEIC ACID MOLECULE HAVING BINDING AFFINITY TO A TARGET MOLECULE AND A METHOD FOR GENERATING THE SAME
    • 具有结合亲和性的目标分子的核酸分子及其产生方法
    • WO2012095303A1
    • 2012-07-19
    • PCT/EP2012/000089
    • 2012-01-10
    • NOXXON PHARMA AGJAROSCH, FlorianKLUSSMANN, SvenSELL, SimonePURSCHKE, WernerMAASCH, ChristianVATER, AxelHÖHLIG, Kai
    • JAROSCH, FlorianKLUSSMANN, SvenSELL, SimonePURSCHKE, WernerMAASCH, ChristianVATER, AxelHÖHLIG, Kai
    • C12N15/11C12N15/115
    • C12N15/115C12N15/102C12N15/111C12N2310/16C12N2310/32C12N2320/13C12N2330/31G01N33/5308G01N2400/10G01N2500/04
    • The present invention is related to a method for generating a nucleic acid molecule capable of binding to a target molecule comprising the following steps: a) providing a reference nucleic acid molecule, wherein the reference nucleic acid molecule is capable of binding to the target molecule and wherein the reference nucleic acid molecule comprises a sequence of nucleotides, wherein the sequence of nucleotides comprises n nucleotides; b) preparing a first level derivative of the reference nucleic acid molecule, wherein the first level derivative of the reference nucleic acid molecule differs from the reference nucleic acid molecule at one nucleotide position, wherein the first level derivative is prepared by replacing the ribonucleotide at the one nucleotide position by a 2'-deoxyribonucleotide in case the reference nucleic acid has a ribonucleotide at the nucleotide position and wherein the first level derivative is prepared by replacing the 2'-deoxyribonucleotide at the one nucleotide position by a ribonucleotide in case the reference nucleic acid has a 2'-deoxyribonucleotide at the nucleotide position and wherein the nucleotide position at which the replacement is made is the modified nucleotide position; and c) repeating step b) for each nucleotide position of the reference nucleic acid molecule, thus preparing a group of first level derivatives of the reference nucleic acid molecule, wherein the group of first level derivatives of the reference nucleic acid molecule consists of n first level derivatives, wherein each of the first level derivatives of the reference nucleic acid molecule differs from the reference nucleic acid molecule by a single nucleotide replacement and wherein each of the first level derivatives of the reference nucleic acid molecule has a single modified nucleotide position which is different from the single modified nucleotide of all of the single modified nucleotide positions of the other first level derivatives of the group of first level derivatives of the reference nucleic acid molecule.
    • 本发明涉及产生能够结合靶分子的核酸分子的方法,该方法包括以下步骤:a)提供参照核酸分子,其中参考核酸分子能够结合靶分子和 其中所述参考核酸分子包含核苷酸序列,其中所述核苷酸序列包含n个核苷酸; b)制备参考核酸分子的一级衍生物,其中参考核酸分子的第一级衍生物在一个核苷酸位置与参考核酸分子不同,其中第一级衍生物通过将核糖核酸 在参考核酸在核苷酸位置具有核糖核苷酸的情况下,通过2'-脱氧核糖核苷酸的一个核苷酸位置,并且其中第一级衍生物是通过核糖核苷酸替换核糖核苷酸的2'-脱氧核糖核苷酸而制备的, 酸在核苷酸位置具有2'-脱氧核糖核苷酸,其中进行置换的核苷酸位置是修饰的核苷酸位置; 和c)对参考核酸分子的每个核苷酸位置重复步骤b),从而制备参考核酸分子的一级第一级衍生物,其中参考核酸分子的一级衍生物组由n个第一 其中参考核酸分子的每个第一级衍生物通过单核苷酸替换与参考核酸分子不同,并且其中参考核酸分子的每个第一级衍生物具有单个修饰的核苷酸位置,其为 与参考核酸分子的第一级衍生物组的其他第一级衍生物的所有单一修饰的核苷酸位置的单个修饰的核苷酸不同。