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    • 2. 发明授权
    • Codon optimized synthetic plasmids
    • 密码子优化的合成质粒
    • US07316925B2
    • 2008-01-08
    • US10619939
    • 2003-07-15
    • Ruxandra Draghia-AkliRonald V. AbruzzeseDouglas R. Kern
    • Ruxandra Draghia-AkliRonald V. AbruzzeseDouglas R. Kern
    • C12N15/85C07H21/04A61K48/00
    • C12N15/67A61K48/00C07K14/60C12N15/85C12N2830/008C12N2830/15C12N2840/20C12N2840/203
    • One aspect of the current invention is an optimized synthetic mammalian expression plasmid (e.g. pAV0201). This new plasmid comprise a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5′ untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, and an origin of replication. The first-operatively-linked arrangement and the second-operatively-linked arrangement comprise a circular structure of the codon optimized synthetic mammalian expression plasmid.
    • 本发明的一个方面是优化的合成哺乳动物表达质粒(例如pAV0201)。 该新质粒包含治疗元件和复制元件。 新质粒的治疗元件包含真核启动子; 5'非翻译区(“UTR”); 密码子优化的真核治疗基因序列; 和聚腺苷酸化信号。 该质粒的治疗元件可操作地连接并位于第一可操作连接的布置中。 此外,优化的合成哺乳动物表达质粒包含复制元件,其中复制元件可操作地连接并位于第二可操作连接的布置中。 复制元件包括选择性标记基因启动子,核糖体结合位点和复制起点。 第一操作连接的排列和第二操作连接的排列包括密码子优化的合成哺乳动物表达质粒的圆形结构。
    • 3. 发明授权
    • Electrode assembly for constant-current electroporation and use
    • 用于恒流电穿孔和使用的电极组件
    • US07664545B2
    • 2010-02-16
    • US11495021
    • 2006-07-28
    • Allan WesterstenWilliam R. WilkinsonRuxandra Draghia-AkliRobert H. CarpenterDouglas R. Kern
    • Allan WesterstenWilliam R. WilkinsonRuxandra Draghia-AkliRobert H. CarpenterDouglas R. Kern
    • A61N1/30
    • A61N1/327
    • The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a non-symmetrically arranged plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes. The applied constant-current electrical pulse facilitates the introduction of the macromolecule into the cell between the plurality of electrodes. Cell death due to overheating of cells is minimized by limiting the power dissipation in the tissue by virtue of constant-current pulses.
    • 本发明涉及一种模块化电极系统及其用途,用于促进将大分子引入体内或选定组织中的细胞中。 模块化电极系统包括非对称布置的多个针电极; 皮下注射针 电连接器,其从可编程恒定电流脉冲控制器提供到多个针电极的导电连接; 和电源。 在本发明的优选实施例中,操作者可以抓住安装在支撑结构上的多个针电极并将其牢固地插入到身体或植物中的所选择的组织中。 然后通过皮下注射针将大分子递送到选定的组织中。 可编程恒定电流脉冲控制器被激活,并且多个针电极施加恒流电脉冲。 施加的恒流电脉冲有助于将大分子引入多个电极之间的电池中。 由于通过恒定电流脉冲限制组织中的功率消耗,使由于细胞过热引起的细胞死亡被最小化。
    • 7. 发明申请
    • CODON OPTIMIZED SYNTHETIC PLASMIDS
    • CODON优化合成PLASMIDS
    • US20080194511A1
    • 2008-08-14
    • US11941876
    • 2007-11-16
    • Ruxandra Draghia-AkliRonald V. AbruzzeseDouglas R. Kern
    • Ruxandra Draghia-AkliRonald V. AbruzzeseDouglas R. Kern
    • A61K31/711
    • C12N15/67A61K48/00C07K14/60C12N15/85C12N2830/008C12N2830/15C12N2840/20C12N2840/203
    • One aspect of the current invention is an optimized synthetic mammalian expression plasmid (e.g. pAV0201). This new plasmid comprise a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5′ untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, and an origin of replication. The first-operatively-linked arrangement and the second-operatively-linked arrangement comprise a circular structure of the codon optimized synthetic mammalian expression plasmid.
    • 本发明的一个方面是优化的合成哺乳动物表达质粒(例如pAV0201)。 该新质粒包含治疗元件和复制元件。 新质粒的治疗元件包含真核启动子; 5'非翻译区(“UTR”); 密码子优化的真核治疗基因序列; 和聚腺苷酸化信号。 该质粒的治疗元件可操作地连接并位于第一可操作连接的布置中。 此外,优化的合成哺乳动物表达质粒包含复制元件,其中复制元件可操作地连接并位于第二可操作连接的布置中。 复制元件包括选择性标记基因启动子,核糖体结合位点和复制起点。 第一操作连接的排列和第二操作连接的排列包括密码子优化的合成哺乳动物表达质粒的圆形结构。
    • 8. 发明授权
    • Electrode assembly for constant-current electroporation and use
    • 用于恒流电穿孔和使用的电极组件
    • US07245963B2
    • 2007-07-17
    • US10360768
    • 2002-03-07
    • Ruxandra Draghia-AkliRobert H. CarpenterDouglas R. KernAllan WesterstenWilliam R. Wilkinson
    • Ruxandra Draghia-AkliRobert H. CarpenterDouglas R. KernAllan WesterstenWilliam R. Wilkinson
    • A61N1/30
    • A61N1/327
    • The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes. The applied constant-current electrical pulse facilitates the introduction of the macromolecule into the cell between the plurality of electrodes. Cell death due to overheating of cells is minimized by limiting the power dissipation in the tissue by virtue of constant-current pulses.
    • 本发明涉及一种模块化电极系统及其用途,用于促进将大分子引入体内或选定组织中的细胞中。 模块化电极系统包括多个针电极; 皮下注射针 电连接器,其从可编程恒定电流脉冲控制器提供到多个针电极的导电连接; 和电源。 在本发明的优选实施例中,操作者可以抓住安装在支撑结构上的多个针电极并将其牢固地插入到身体或植物中的所选择的组织中。 然后通过皮下注射针将大分子递送到选定的组织中。 可编程恒定电流脉冲控制器被激活,并且多个针电极施加恒流电脉冲。 施加的恒流电脉冲有助于将大分子引入多个电极之间的电池中。 由于通过恒定电流脉冲限制组织中的功率消耗,使由于细胞过热引起的细胞死亡被最小化。