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    Use of viral CIS-acting post-transcriptional regulatory sequences to increase expression of intronless genes containing near-consensus splice sites
    3.
    发明授权
    Use of viral CIS-acting post-transcriptional regulatory sequences to increase expression of intronless genes containing near-consensus splice sites 失效
    使用病毒CIS作用的转录后调控序列增加含有近似共有剪接位点的内含子基因的表达

    公开(公告)号：US5744326A

    公开(公告)日：1998-04-28

    申请号：US683839

    申请日：1996-03-11

    Applicant: Charles R. Ill ,  Scott Bidlingmaier

    Inventor： Charles R. Ill ,  Scott Bidlingmaier

    IPC: C12N15/09 ,  C07K14/755 ,  C12N9/64 ,  C12N15/12 ,  C12N15/85 ,  C12N15/63 ,  C07H21/04 ,  C12N15/79

    CPC classification number: C12N9/644 ,  C07K14/755 ,  C12N15/85 ,  C12Y304/21022 ,  C12N2800/108 ,  C12N2830/42 ,  C12N2830/48 ,  C12N2840/44

    Abstract: Expression vectors are disclosed comprising intronless genes containing one or more near consensus splice sequences and one or more copies of a viral cis-acting post-transcriptional regulatory element which is transcribed along with the gene and causes export of the gene transcript from the nucleus into the cytoplasm of the cell. In a preferred embodiment, the vectors are targeted for delivery to specific cells in the form of a molecular complex made up of the plasmid releasably linked to a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. Use of viral cis-acting post-transcriptional regulatory elements as disclosed can increase expression of intronless genes with near-consensus splice sites.

    Abstract translation: 公开了表达载体，其包含含有一个或多个近似共有剪接序列的内含子基因和与基因一起转录的病毒顺式作用后转录调控元件的一个或多个拷贝，并导致将基因转录物从细胞核导出到 细胞的细胞质。 在优选的实施方案中，载体被靶向以分子复合物形式递送至特定细胞，该分子复合物由与核酸结合剂可释放地连接的质粒和与细胞表面上的组分结合的配体组成。 所公开的病毒顺式作用的转录后调控元件的使用可以增加具有近似共有剪接位点的内含子基因的表达。

    Vectors and genes exhibiting increased expression
    5.
    发明授权
    Vectors and genes exhibiting increased expression 失效
    载体和表达增加的基因

    公开(公告)号：US06642028B1

    公开(公告)日：2003-11-04

    申请号：US09205817

    申请日：1998-12-04

    Applicant: Charles R. Ill ,  Jose E. N. Gonzales ,  Claire Q. Yang ,  Scott Bidlingmaier

    Inventor： Charles R. Ill ,  Jose E. N. Gonzales ,  Claire Q. Yang ,  Scott Bidlingmaier

    IPC: C12P2100

    CPC classification number: C07K14/755 ,  A61K48/00 ,  C12N15/67 ,  C12N15/85 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/42 ,  C12N2830/48 ,  C12N2830/85 ,  C12N2840/44 ,  C12N2840/445

    Abstract: Novel genes and vectors exhibiting increased expression and novel splicing patterns are disclosed. The gene can comprise one or more consensus or near consensus splice sites which have been corrected. The gene can alternatively or additionally comprise one or more introns within coding or noncoding sequences. The gene can still further comprise modified 5′ and/or 3′ untranslated regions optimized to provide high levels and duration of tissue-specific expression. In one embodiment, the gene comprises the coding region of a full-length Factor VIII gene modified by adding an intron within the portion of the gene encoding the &bgr;-domain, so that the gene is expressed as a &bgr;-domain deleted Factor VIII protein. The novel Factor VIII gene can also be modified to correct one or more consensus or near consensus splice sites within or outside of the coding region.

    Abstract translation: 公开了表现出增加的表达和新的剪接模式的新型基因和载体。 该基因可以包含已被校正的一个或多个共有或近似一致的剪接位点。 该基因可以替代地或另外包含编码或非编码序列内的一个或多个内含子。 该基因还可以进一步包含经过优化以提供组织特异性表达的高水平和持续时间的经修饰的5'和/或3'非翻译区。 在一个实施方案中，该基因包含通过在编码β-结构域的基因的部分内添加内含子而修饰的全长因子VIII基因的编码区，使得该基因被表达为β域缺失的因子VIII蛋白 。 也可以修饰新的因子VIII基因以修正编码区内或外的一个或多个共有或近似的共有剪接位点。

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