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    • 6. 发明申请
    • BCL-2 DNAZYMES
    • WO2002099090A1
    • 2002-12-12
    • PCT/AU2002/000739
    • 2002-06-07
    • JOHNSON & JOHNSON RESEARCH PTY LTDSUN, Lun-QuanWANG, LiTURNER, Rachel, JaneSARAVOLAC, Edward, GeorgeDASS, Crispin, Rajnish
    • SUN, Lun-QuanWANG, LiTURNER, Rachel, JaneSARAVOLAC, Edward, GeorgeDASS, Crispin, Rajnish
    • C12N9/00
    • C12N15/1135C12N2310/12
    • The present invention provides DNAzymes which specifically cleaves mRNA transcribed from a member of the bcl-2 gene family selected from the group consisting of bcl-2, bcl-xl, bcl-w, bfl-1, brag-1, Mcl-1 and A1. The DNAzymes comprise (a) a catalytic domain that has the nucleotide sequence GGCTAGCTACAACGA (SEQ ID NO.1) and cleaves mRNA at any purine: pyrimidine cleavage site at which it is directed, (b) a binding domain contiguous with the 5' end of the catalytic domain, and (c) another binding domain contiguous with the 3' end of the catalytic domain. The binding domains are complementary to, and therefore hybridise with, the two regions immediately flanking the purine residue of the cleavage site within the bcl-2 gene family mRNA, at which DNAzyme-catalysed cleavage is desired. Each binding domain is at least six nucleotides in length, and both binding domains have a combined total length of at least 14 nucleotides.
    • 本发明提供了特异性切割从bcl-2基因家族成员转录的mRNA的DNA酶,其选自bcl-2,bcl-xl,bcl-w,bfl-1,brag-1,Mcl-1和 A1。 DNAzymes包含(a)具有核苷酸序列GGCTAGCTACAACGA(SEQ ID NO.1)的催化结构域,并在任何嘌呤:其所针对的嘧啶切割位点处切割mRNA,(b)与5'端连接的结合结构域 的催化结构域,和(c)与催化结构域的3'末端相邻的另一个结合结构域。 结合结构域与bcl-2基因家族mRNA内的切割位点的嘌呤残基紧邻的两个区域互补,并因此杂交,需要DNA酶催化切割。 每个结合结构域的长度至少为6个核苷酸,两个结合结构域的总长度至少为14个核苷酸。