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公开(公告)号：US5562904A
公开(公告)日：1996-10-08
申请号：US278550
申请日：1994-07-21
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K45/00 , A61K48/00 , A61P43/00 , C07K16/18 , C12P21/08 , B61K39/395
摘要： Methods and compositions are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The administration of soluble complement inhibitor molecules to body fluids prevents the complement mediated inactivation of the retroviral vector particles, and provides a safety mechanism for such gene therapy procedures, as the action of soluble complement inhibitors is transient, and any retroviral vector particles present after the return of uninhibited complement activity will be inactivated. Preferred soluble complement inhibitors for use in the practice of the present invention include complement inhibitory anti-complement component mAbs (including complement inhibitory anti C5 antibodies).
摘要翻译： 提供了方法和组合物，用于促进涉及在含补体的体液存在下用逆转录病毒载体颗粒转导靶细胞的基因治疗方法。 向体液施用可溶性补体抑制剂分子可防止补体介导的逆转录病毒载体颗粒的失活，并为此类基因治疗程序提供安全机制，因为可溶性补体抑制剂的作用是暂时的，并且任何逆转录病毒载体颗粒存在于 不受限制的补体活动的返回将被灭活。 用于实施本发明的优选的可溶性补体抑制剂包括补体抑制性抗补体成分mAb（包括补体抑制性抗C5抗体）。
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公开(公告)号：US5643770A
公开(公告)日：1997-07-01
申请号：US278630
申请日：1994-07-21
申请人： James M. Mason , Stephen P. Squinto
发明人： James M. Mason , Stephen P. Squinto
IPC分类号： A61K48/00 , C12N15/48 , C12N15/867 , C12N15/86 , C07K14/15
CPC分类号： C12N15/86 , C07K14/005 , A61K48/00 , C12N2740/13022 , C12N2740/13043
摘要： Modified retroviral vector particles and modified retroviral producer cells producing such particles are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The modifications involve genetic alterations to effect the expression by these cells and particles of complement inhibitor activity. The genetic alterations involve the introduction of nucleic acid expression constructs directing the expression of retroviral SU(gp70)/complement inhibitor chimeric proteins into cells from which the producer cells are derived.
摘要翻译： 提供了产生这种颗粒的修饰的逆转录病毒载体颗粒和修饰的逆转录病毒产生细胞，用于促进涉及在含补体的体液存在下用逆转录病毒载体颗粒转导靶细胞的基因治疗方法。 修饰涉及遗传改变以影响这些细胞和补体抑制剂活性颗粒的表达。 遗传改变涉及将逆转录病毒SU（gp70）/补体抑制剂嵌合蛋白的表达引入导入生产细胞的细胞中的核酸表达构建体。
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公开(公告)号：US09089117B2
公开(公告)日：2015-07-28
申请号：US12322262
申请日：2009-01-30
申请人： Daniel A. Grande , James M. Mason
发明人： Daniel A. Grande , James M. Mason
CPC分类号： A01K67/0271 , A61K38/1841 , A61K38/1858 , A61K38/1875 , A61K38/30 , A61K47/6901 , A61L27/38 , A61L27/56
摘要： Provided are tissue scaffolds colonized by vertebrate cells expressing a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.
摘要翻译： 提供的是由表达转基因生物活性分子的脊椎动物细胞定植的组织支架，其中脊椎动物细胞不能发生有丝分裂。 还提供了在哺乳动物中培养组织的方法和使用组织支架将转基因生物活性分子递送至哺乳动物的组织的方法。 另外，提供了制作组织支架的方法。
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公开(公告)号：US20100008967A1
公开(公告)日：2010-01-14
申请号：US12322262
申请日：2009-01-30
申请人： Daniel A. Grande , James M. Mason
发明人： Daniel A. Grande , James M. Mason
CPC分类号： A01K67/0271 , A61K38/1841 , A61K38/1858 , A61K38/1875 , A61K38/30 , A61K47/6901 , A61L27/38 , A61L27/56
摘要： Provided are tissue scaffolds colonized by vertebrate cells expressing a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.
摘要翻译： 提供的是由表达转基因生物活性分子的脊椎动物细胞定植的组织支架，其中脊椎动物细胞不能发生有丝分裂。 还提供了在哺乳动物中培养组织的方法和使用组织支架将转基因生物活性分子递送至哺乳动物的组织的方法。 另外，提供了制作组织支架的方法。
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公开(公告)号：US5466603A
公开(公告)日：1995-11-14
申请号：US196626
申请日：1994-02-15
申请人： Brian W. Meehan , Uwe Heine , James M. Mason
发明人： Brian W. Meehan , Uwe Heine , James M. Mason
CPC分类号： B01L7/02
摘要： A temperature regulated hybridization chamber which includes an outer container which defines a first chamber for receiving a first fluid having a predetermined temperature. The hybridization chamber includes an inner container having a generally horizontal bottom wall with a periphery and an inner container side wall extending generally upwardly from the periphery of the inner container bottom wall. The inner container bottom wall and the inner container side wall define a second chamber for receiving a second fluid. The inner container is positioned within the first chamber with the inner container bottom wall and the inner container side wall being spaced from the outer container bottom wall and the outer container side wall, respectively, such that when the first fluid is positioned within the first chamber the first fluid is in engagement with the inner container bottom wall and inner container side wall. A drain conduit is in fluid communication with the second chamber for removing the second fluid from the second chamber. The drain conduit is positioned such that the second fluid flows through the drain conduit due to the force of gravity such that the second fluid in the inner chamber is maintained at a temperature which is about equal to the predetermined temperature of the first fluid.
摘要翻译： 温度调节杂交室，其包括限定用于接收具有预定温度的第一流体的第一室的外容器。 杂交室包括具有大致水平的底壁的内部容器，其具有周边和从容器内壁的周边大致向上延伸的内部容器侧壁。 内容器底壁和内容器侧壁限定用于接收第二流体的第二室。 内容器位于第一室内，内容器底壁和内容器侧壁分别与外容器底壁和外容器侧壁间隔开，使得当第一流体位于第一室内时 第一流体与内容器底壁和内容器侧壁接合。 排水管道与第二室流体连通，用于从第二室移除第二流体。 排水管被定位成使得第二流体由于重力而流过排水管，使得内室中的第二流体保持在大约等于第一流体的预定温度的温度。
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6.发明授权公开(公告)号：US06398816B1
公开(公告)日：2002-06-04
申请号：US09489756
申请日：2000-01-21
IPC分类号： A61F236
CPC分类号： A61K38/1875 , A61K48/00
摘要： A method for enhancing and/or increasing the efficiency of repair of tissues, primarily bone or cartilage, using genetically engineered cells has been developed. In the preferred embodiment, mesenchymal stem cells are isolated from periosteum tissue, and transfected with the gene encoding a growth factor for the particular cell type to be repaired. For example, for repair of bone, a gene (or genes) encoding bone morphogenic protein is transfected into periosteal cells. The transfected periosteal cells then express the bone morphogenic protein in culture to promote bone repair as a function of the expressed bone morphogenic protein. Cells can be transfected using any appropriate means, including viral vectors, as shown by the example, chemical transfectants, or physico-mechanical methods such as electroporation and direct diffusion of DNA. Genes can encode any useful protein, for example, a specific growth factor, morphogenesis factor, a structural protein, or a cytokine which enhances the temporal sequence of wound repair, alters the rate of proliferation, increases the metabolic synthesis of extracellular matrix proteins, or directs phenotypic expression in endogenous cell populations. Representative genes encoding proteins include bone growth factor genes, cartilage growth factor genes, nerve growth factor genes, and general growth factors important in wound healing, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), basic fibroblast growth factor (FGF), endothelial derived growth supplement.
摘要翻译： 已经开发了使用基因工程细胞增强和/或增加组织，主要是骨或软骨的修复效率的方法。 在优选的实施方案中，从骨膜组织中分离间充质干细胞，并用编码待修复的特定细胞类型的生长因子的基因转染。 例如，为了修复骨，将编码骨形态发生蛋白的基因（或基因）转染到骨膜细胞中。 转染的骨膜细胞然后在培养物中表达骨形态发生蛋白，以促进骨修复作为表达的骨形态发生蛋白的函数。 可以使用任何适当的方式，包括病毒载体，如实施例所示，化学转染子，或物理 - 机械方法如DNA的电穿孔和直接扩散来转染细胞。 基因可以编码任何有用的蛋白质，例如特异性生长因子，形态发生因子，结构蛋白质或细胞因子，其增强伤口修复的时间序列，改变增殖速率，增加细胞外基质蛋白质的代谢合成，或 指导内源性细胞群体中的表型表达。 编码蛋白质的代表性基因包括骨生长因子基因，软骨生长因子基因，神经生长因子基因和伤口愈合中重要的一般生长因子，例如血小板衍生生长因子（PDGF），血管内皮生长因子（VEGF） 类似生长因子（IGF-1），表皮生长因子（EGF），碱性成纤维细胞生长因子（FGF），内皮衍生生长补体。
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公开(公告)号：US5985655A
公开(公告)日：1999-11-16
申请号：US484126
申请日：1995-06-07
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , C07K14/15 , C07K14/47 , C12N5/10 , C12N15/58 , C12N15/867 , C12N15/87 , C12N15/63
CPC分类号： C07K14/005 , C07K14/473 , C12N15/86 , C12N15/87 , C07K2319/00 , C07K2319/75 , C12N2740/13022 , C12N2740/13043 , C12N2740/13045 , C12N2740/16222 , C12N2810/60 , C12N2810/6054 , C12N2810/80
摘要： A vector particle (e.g., a retroviral vector particle) containing a chimeric envelope includes a receptor binding region that binds to a receptor of a target cell. The receptor of the target cell is other than the amphotropic cell receptor. The receptor binding region may be a receptor binding region of a human virus. A portion of the envelope gene may be deleted and the deleted portion is replaced with another receptor binding region or ligand. Such vector particles are targetable to a desired target cell or tissue, and may be administered directly to the desired target cell or tissue as part of a gene therapy procedure, or administered directly into the patient.
摘要翻译： 含有嵌合包膜的载体颗粒（例如，逆转录病毒载体颗粒）包括与靶细胞的受体结合的受体结合区。 靶细胞的受体不仅是独立细胞受体。 受体结合区可以是人病毒的受体结合区。 可以缺失一部分包膜基因，并用另一个受体结合区或配体代替缺失部分。 这样的载体颗粒可靶向所需的靶细胞或组织，并且可以作为基因治疗程序的一部分直接施用于期望的靶细胞或组织，或直接施用于患者体内。
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公开(公告)号：US4940581A
公开(公告)日：1990-07-10
申请号：US233999
申请日：1988-08-15
申请人： James M. Mason , David D. Pifer
发明人： James M. Mason , David D. Pifer
CPC分类号： A01N1/0221 , A61K35/19
摘要： A method for preserving blood platelets by freezing the platelets in contact with a cryoprotectant solution containing a sufficient quantity of prostacyclin for the substantially complete inhibition of platelet function and having a pH which promotes the preservation of the platelets and reconstituting the platelets for infusion.
摘要翻译： 通过冷冻与含有足够量的前列环素的冷冻保护剂溶液接触的血小板来维持血小板的方法，用于基本上完全抑制血小板功能并具有促进血小板保存并重建血小板以进行输注的pH。
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公开(公告)号：US06649588B1
公开(公告)日：2003-11-18
申请号：US09679971
申请日：2000-10-05
申请人： Siamak Tabibzadeh , James M. Mason
发明人： Siamak Tabibzadeh , James M. Mason
IPC分类号： A61K3800
CPC分类号： A61K38/1841 , C07K14/47 , C12Q1/6883 , Y10S514/899
摘要： The present invention provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with an amount of ebaf or an ebaf analogue. The present invention further provides a method for treating a condition associated with overactivity of TGF-&bgr;, particularly fibrosis, a defect in cell proliferation, or a coagulation defect. The present invention also provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with a modulator of ebaf expression, or a modulator of expression of an ebaf analogue. The present invention is further directed to a method for treating fibrosis in a subject in need of treatment, comprising administering to the subject an amount of ebaf or an ebaf analogue effective to treat the fibrosis. Finally, the present invention provides a method for treating a defect in cell proliferation in a subject in need of treatment, comprising administering to the subject an amount of ebaf or an ebaf analogue effective to treat the defect in cell proliferation.
摘要翻译： 本发明提供了一种抑制TGF-β活性的方法，包括使表达TGF-β的组织与一定量的ebaf或ebaf类似物接触。 本发明还提供了用于治疗与TGF-β的过度活跃性，特别是纤维化，细胞增殖缺陷或凝血缺陷相关的病症的方法。 本发明还提供了一种抑制TGF-β活性的方法，包括使表达TGF-β的组织与ebaf表达的调节剂或ebaf类似物的表达调节剂接触。 本发明还涉及在需要治疗的受试者中治疗纤维化的方法，其包括对受试者施用一定量的有效治疗纤维化的ebaf或ebaf类似物。 最后，本发明提供一种治疗需要治疗的受试者的细胞增殖缺陷的方法，其包括对受试者施用一定量的有效治疗细胞增殖缺陷的ebaf或ebaf类似物。
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公开(公告)号：US06503501B1
公开(公告)日：2003-01-07
申请号：US09374909
申请日：1999-08-13
IPC分类号： A61K4800
CPC分类号： C07K14/005 , C07K14/473 , C07K2319/00 , C07K2319/75 , C12N15/86 , C12N15/87 , C12N2740/13022 , C12N2740/13043 , C12N2740/13045 , C12N2740/16222 , C12N2810/60 , C12N2810/6054 , C12N2810/80
摘要： A vector particle (eg., a retroviral vector particle) containing a chimeric envelope includes a receptor binding region that binds to a receptor of a target cell. The receptor of the target cell is other than the amphotropic cell receptor. The receptor binding region may be a receptor binding region of a human virus. A portion of the envelope gene may be deleted and the deleted portion is replaced with another receptor binding region or ligand. Such vector particles are targetable to a desired target cell or tissue, and may be administered directly to the desired target cell or tissue as part of a gene therapy procedure, or administered directly into the patient.
摘要翻译： 含有嵌合包膜的载体颗粒（例如，逆转录病毒载体颗粒）包括与靶细胞的受体结合的受体结合区。 靶细胞的受体不仅是独立细胞受体。 受体结合区可以是人病毒的受体结合区。 可以缺失一部分包膜基因，并用另一个受体结合区或配体代替缺失部分。 这样的载体颗粒可靶向所需的靶细胞或组织，并且可以作为基因治疗程序的一部分直接施用于期望的靶细胞或组织，或直接施用于患者体内。
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