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    • 5. 发明申请
    • USE OF TRANS-ACTIVATION AND CIS-ACTIVATION TO MODULATE THE PERSISTENCE OF EXPRESSION OF A TRANSGENE
    • 使用转移激活和CIS激活来调节转基因表达的持续性
    • WO0034496A3
    • 2000-09-14
    • PCT/US9928637
    • 1999-12-03
    • GENVEC INCBROUGH DOUGLAS EKOVESDI IMRE
    • BROUGH DOUGLAS EKOVESDI IMRE
    • C12N15/09A61K35/76A61K38/00A61K48/00A61P31/00A61P35/00C07K14/035C07K14/075C12N15/35C12N15/63C12N15/861C12N15/38
    • C12N15/86C07K14/005C12N15/63C12N2710/10322C12N2710/10345C12N2710/16622C12N2830/60C12N2840/60
    • Provided are methods of modulating the persistence of the expression in a cell of a transgene, such as a transgene in a non-Herpes vector or in at least E4 DELTA adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gene encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (ii) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or the system further comprises a vector, in which case the vector comprises the transgene. Another method comprises contacting the cell with an at least E4 DELTA adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, wherein the trans-acting factor modulates the persistence of expression of the transgene and the gene encoding the trans-acting factor is not from the E4 region of an adenovirus. Yet another method comprises contacting a cell simultaneously or sequentially with (i) an at least E4 DELTA adenoviral vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. Also provided is a system for modulating the persistence of expression of a transgene in an at least E4 DELTA adenoviral vector, which system comprises (i) an at least E4 DELTA adenoviral vector comprising a transgene and (ii) a gene encoding a trans-acting factor, wherein the gene encoding the trans-acting factor is not from the E4 region of an adenovirus, the trans-acting factor modulates the persistence of expression of the transgene, and either the at least E4 DELTA adenoviral vector comprises the gene encoding the trans-acting factor or the system comprises a viral vector, in which case the viral vector comprises the gene encoding the trans-acting factor.
    • 提供了调节转基因(例如非疱疹病毒载体或至少E4Δ腺病毒载体中的转基因)细胞中表达持续存在的方法,以及相关系统。 一种方法包括使细胞与包含和表达编码HSV ICP0的基因的非疱疹载体接触,于是HSV ICP0的表达调节了转基因表达的持续性。 进一步提供了用于调节转基因表达持续存在的系统,所述系统包含非疱疹载体,所述非疱疹载体包含(i)编码HSV ICP0的基因和(ii)转基因,其中HSV ICP0调节所述转基因表达的持续存在 转基因,并且非疱疹载体包含转基因或该系统还包含载体,在这种情况下,载体包含转基因。 另一种方法包括使细胞与包含(i)转基因和(ii)编码反式作用因子的基因的至少E4Δ腺病毒载体接触,其中反式作用因子调节转基因和基因表达的持续存在 编码反式作用因子不是来自腺病毒的E4区。 另一种方法包括将细胞同时或依次与(i)包含转基因的至少E4Δ腺病毒载体和(ii)包含编码反式作用因子的基因的病毒载体接触,所述反式作用因子不来自 腺病毒,并调节转基因表达的持续存在。 还提供了用于调节至少E4ΔTA腺病毒载体中转基因表达的持续存在的系统,所述系统包含(i)包含转基因的至少E4ΔΔ腺病毒载体和(ii)编码反式作用的基因 因子,其中编码反式作用因子的基因不是来自腺病毒的E4区,反式作用因子调节转基因表达的持久性,并且至少E4ΔΔ腺病毒载体包含编码反式作用因子的基因 或该系统包含病毒载体,在这种情况下病毒载体包含编码反式作用因子的基因。
    • 9. 发明申请
    • METHODS OF GENE THERAPY FOR TREATING DISORDERS OF THE EAR BY ADMINISTERING A VECTOR ENCODING AN ATONAL-ASSOCIATED FACTOR
    • 通过管理编码相关因子的矢量来治疗耳朵疾病的基因治疗方法
    • WO2004076626A3
    • 2004-10-28
    • PCT/US2004004891
    • 2004-02-19
    • GENVEC INCBROUGH DOUGLAS E
    • BROUGH DOUGLAS E
    • A61K38/00A61K48/00A61P27/00C12N15/861C12N15/86
    • A61K38/17A61K38/00A61K48/005C07K14/4702C12N7/00C12N15/86C12N2501/60C12N2710/10343
    • The invention is directed to a method of changing the sensory perception of an animal. The method comprises administering an expression vector comprising a nucleic acid sequence encoding an atonal-associated factor, which is expressed to produce the atonal-associated factor resulting in generation of hair cells that allow perception of stimuli in the inner ear. Also provided is a method of generating a hair cell in differentiated sensory epithelia in vivo. The method comprises contacting differentiated sensory epithelial cells with an adenoviral vector (a) deficient in one or more replication-essential gene functions of the El region and E4 region, (b) comprising a spacer in the E4 region, and (c) comprising a nucleic acid sequence encoding an atonal-associated factor. The nucleic acid sequence is expressed to produce the atonal-associated factor such that a hair cell is generated. An adenoviral vector encoding an atonal-associated factor also is provided.
    • 本发明涉及一种改变动物的感觉知觉的方法。 所述方法包括施用包含编码无关联因子的核酸序列的表达载体,所述核酸序列被表达以产生导致产生能够感知内耳中的刺激的毛细胞的无关性因子。 还提供了一种在体内在分化感觉上皮细胞中产生毛细胞的方法。 该方法包括使分化的感觉上皮细胞与E1区和E4区的一个或多个复制必需基因功能缺陷的腺病毒载体(a)接触,(b)在E4区中包含间隔基,和(c)包含 编码无关联因子的核酸序列。 表达核酸序列以产生无关联因子,使得产生毛细胞。 还提供了编码无关联因子的腺病毒载体。