Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
    43.
    发明授权
    Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines 失效
    增强的三螺旋和双螺旋形成与含有修饰嘧啶的低聚物

    公开(公告)号:US06962783B2

    公开(公告)日:2005-11-08

    申请号:US10024818

    申请日:2001-12-18

    摘要: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

    摘要翻译: 公开了与仅含有常规碱的低聚物相比,具有增强形成双链体或三链体的能力的新型低聚物。 低聚物含有5-(1-丙炔基)尿嘧啶,5-(1-丙炔基)胞嘧啶或相关类似物的碱基。 本发明的寡聚体能够(i)通过在生理pH下偶联到目标DNA双链体的主要沟槽中或(ii)通过结合单链DNA形成双链体,形成具有各种靶序列的病毒或致癌基因序列的三链体 或由靶基因编码的RNA。 本发明的寡聚体可以并入药学上可接受的载体中,并且可以被构建成具有任何所需的序列,条件是序列通常包括用本发明的类似物代替的一个或多个碱基。 本发明的组合物可以用作药剂来治疗由病毒引起的各种疾病,并且可以用于诊断目的以检测病毒或疾病状况。

    Modified internucleoside linkages (II)
    45.
    发明授权
    Modified internucleoside linkages (II) 失效
    修饰的核苷间键(II)

    公开(公告)号:US06410702B1

    公开(公告)日:2002-06-25

    申请号:US09165883

    申请日:1998-10-02

    IPC分类号: C07H2102

    摘要: The invention relates to novel modified oligonucleotides, the construction thereof, and their use in oligonucleotide-based therapies. More specifically, the invention is to novel oligonucleotides having modified internucleoside linkages which are resistant to nucleases, having enhanced ability to penetrate cells, and which are capable of binding target oligonucleotide sequences in vitro and in vivo. The modified oligonucleotides of the invention are particularly useful in oligonucleotide-based therapies utilizing the modified oligonucleotides to interrupt protein synthesis or transcription or to otherwise inactivate messenger RNA or double stranded DNA.

    摘要翻译: 本发明涉及新型修饰的寡核苷酸,其构建及其在基于寡核苷酸的疗法中的应用。 更具体地,本发明是具有对核酸酶具有抗性的具有修饰的核苷间键的具有增强的穿透细胞的能力并且能够在体外和体内结合靶寡核苷酸序列的新型寡核苷酸。 本发明的经修饰的寡核苷酸特别可用于使用经修饰的寡核苷酸中断蛋白质合成或转录或以其它方式灭活信使RNA或双链DNA的基于寡核苷酸的治疗。

    Methods of using oligomers containing modified pyrimidines
    46.
    发明授权
    Methods of using oligomers containing modified pyrimidines 失效
    使用含有修饰嘧啶的寡聚物的方法

    公开(公告)号:US5830653A

    公开(公告)日:1998-11-03

    申请号:US473481

    申请日:1995-06-07

    摘要: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

    摘要翻译: 公开了与仅含有常规碱的低聚物相比,具有增强形成双链体或三链体的能力的新型低聚物。 低聚物含有5-(1-丙炔基)尿嘧啶,5-(1-丙炔基)胞嘧啶或相关类似物的碱基。 本发明的寡聚体能够(i)通过在生理pH下偶联到目标DNA双链体的主要沟槽中或(ii)通过结合单链DNA形成双链体,形成具有各种靶序列的病毒或致癌基因序列的三链体 或由靶基因编码的RNA。 本发明的寡聚体可以并入药学上可接受的载体中,并且可以被构建成具有任何所需的序列,条件是序列通常包括用本发明的类似物代替的一个或多个碱基。 本发明的组合物可以用作药剂来治疗由病毒引起的各种疾病,并且可以用于诊断目的以检测病毒或疾病状况。

    Oligonucleotide analogs with novel linkages
    50.
    发明授权
    Oligonucleotide analogs with novel linkages 失效
    具有新型键的寡核苷酸类似物

    公开(公告)号:US5264564A

    公开(公告)日:1993-11-23

    申请号:US559957

    申请日:1990-07-30

    申请人: Mark Matteucci

    发明人: Mark Matteucci

    CPC分类号: C07H19/06 C07H19/16 C07H21/00

    摘要: Oligonucleotide analogs wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by an formacetal/ketal type linkage are resistant to nucleases and do not need to exhibit the diastereomerism characteristic of many other oligonucleotide analogs, and thus are capable of strong hybridization to target RNA or DNA. These oligonucleotide analogs are useful in therapies which modulate gene expression using "antisense" or other specifically binding oligomers.

    摘要翻译: 其中相邻核苷酸之间的一个或多个磷酸二酯键被甲缩醛/缩酮型键取代的寡核苷酸类似物对核酸酶具有抗性,并且不需要显示许多其它寡核苷酸类似物的非对映异构体特征,因此能够与靶RNA或 脱氧核糖核酸。 这些寡核苷酸类似物可用于使用“反义”或其他特异性结合寡聚体调节基因表达的治疗。