公开(公告)号：US11814662B2

公开(公告)日：2023-11-14

申请号：US17084432

申请日：2020-10-29

申请人： Progeneer, Inc.

发明人： So Yeon Ahn ,  Srivithya Vellampatti Krishnamoorthy ,  Soong Ho Um ,  Sung Oh ,  Seung Won Shin

IPC分类号： C12P21/00 ,  C07K14/005 ,  C07K14/62 ,  C12N7/00 ,  C12N15/10 ,  C12P21/02 ,  C07K16/28 ,  C07K16/24

CPC分类号： C12P21/00 ,  C07K14/005 ,  C07K14/62 ,  C07K16/241 ,  C12N7/00 ,  C12N2740/16051 ,  C12N2740/16311

摘要： This application provides methods and compositions related to constructing nucleic acid hydrogels (e.g., RNA hydrogels) having repetitive monomer units, each monomer unit includes one or more G-quadruplex sequences. These G-quadruplex sequences cross-link the nucleic acid concatemer such that it self-assembles into a hydrogel under appropriate conditions. In some embodiments, each monomeric unit of the nucleic acid concatemer comprises a coding sequence for polypeptide of interest; and the nucleic acid hydrogel formed by the nucleic acid concatemer can be used for expressing the polypeptide in high quantities. In some embodiments, at least two RNA concatemers comprising G-quadruplex sequences are produced, one further comprising a spacer and the other further comprising a sequence encoding a polypeptide of interest. These two RNA concatemers are combined and self assembled to form a single, wideband RNA hydrogel.

公开(公告)号：US09630995B2

公开(公告)日：2017-04-25

申请号：US13636118

申请日：2011-03-21

申请人： Barbara Ensoli

发明人： Barbara Ensoli

IPC分类号： C07K14/16 ,  A61K39/21 ,  C07K14/005 ,  A61K39/12 ,  A61K39/00

CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/163 ,  C12N2740/16311 ,  C12N2740/16322 ,  C12N2740/16334

摘要： Native Tat, when administered to patients with HIV infection, or who are otherwise immunocompromised, is capable of restoring immune functions so as to recognize recall antigens, and to inhibit replication and key signs of HIV disease and other persistent infections and/or their progression.

公开(公告)号：US20150157597A1

公开(公告)日：2015-06-11

申请号：US14570625

申请日：2014-12-15

申请人： Jun Tan ,  Frank Fernandez ,  Nan Sun ,  Roland D. Shytle ,  Jared Ehrhart

发明人： Jun Tan ,  Frank Fernandez ,  Nan Sun ,  Roland D. Shytle ,  Jared Ehrhart

IPC分类号： A61K31/353 ,  A61K31/4745

CPC分类号： A61K31/353 ,  A01K2267/0318 ,  A61K31/4745 ,  A61K36/82 ,  C12N2740/16111 ,  C12N2740/16311

摘要： The invention relates to treatment of neurodegenerative diseases with JAK/STAT pathway inhibitors to eliminate extracellular cell signaling events leading to cell cycle abrogation and/or apoptosis. Primary neurons were administered neurotoxic proteins, such as gp120, Tat, or gp120 and Tat, with or without IFN-γ added, resulting in neuronal death, and simulated neurodegenerative diseases. The neurodegenerative disease is treated using a JAK/STAT pathway inhibitor, including (-)-epigallocatechin-3-gallate (EGCG), to modulate JAK1 or STAT1 phosphorylation, resulting in resistance to gp120 or Tat neurotoxicity. The invention may be used to treat neurons afflicted with HIV-associated Dementia, multiple sclerosis, Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, or Pick's Disease, and may act in conjunction with antiviral treatment, like HAART.

摘要翻译： 本发明涉及用JAK / STAT途径抑制剂治疗神经变性疾病，以消除导致细胞周期消除和/或凋亡的细胞外细胞信号传导事件。 主要神经元被施用神经毒性蛋白质，例如gp120，Tat或gp120和Tat，加入或不加入IFN-γ，导致神经元死亡和模拟的神经变性疾病。 神经变性疾病使用JAK / STAT途径抑制剂（包括（ - ） - 表没食子儿茶素-3-没食子酸酯（EGCG））来调节JAK1或STAT1磷酸化，导致抗gp120或Tat神经毒性。 本发明可用于治疗患有HIV相关性痴呆，多发性硬化，阿尔茨海默氏病，帕金森病，肌萎缩性侧索硬化或皮克病的神经元，并且可以与抗病毒治疗一起起作用，如HAART。

公开(公告)号：US20140288006A1

公开(公告)日：2014-09-25

申请号：US14201488

申请日：2014-03-07

申请人： Xiao-Jing WANG ,  Qinghong Zhang ,  Yosef Refaeli

发明人： Xiao-Jing WANG ,  Qinghong Zhang ,  Yosef Refaeli

IPC分类号： C07K14/47

CPC分类号： A61K38/18 ,  A61K38/00 ,  A61K38/162 ,  A61K48/005 ,  C07K14/005 ,  C07K14/4702 ,  C07K14/4703 ,  C07K14/475 ,  C07K2319/10 ,  C07K2319/20 ,  C07K2319/23 ,  C12N7/00 ,  C12N2740/16311 ,  C12N2740/16322 ,  C12N2800/22

摘要： The present technology provides methods and compositions for the treatment of inflammatory and/or tissue damage conditions. In particular, the use of Smad7 compositions delivered locally or systemically to a site of inflammation and/or tissue damage is described. Other specific embodiments concern treatment or prevention of side effects caused by radiation and/or chemotherapy, including but not limited to oral and gastric mucositis. Also provided are codon-optimized nucleic acids encoding for Smad7 fusion proteins.

摘要翻译： 本技术提供了用于治疗炎症和/或组织损伤病症的方法和组合物。 特别地，描述了局部或全身地递送到炎症和/或组织损伤部位的Smad7组合物的使用。 其它具体实施方案涉及治疗或预防由放射和/或化疗引起的副作用，包括但不限于口腔和胃粘膜炎。 还提供编码Smad7融合蛋白的密码子优化的核酸。

公开(公告)号：US08512993B2

公开(公告)日：2013-08-20

申请号：US13301147

申请日：2011-11-21

申请人： Pierre Charneau ,  Veronique Zennou ,  Francoise Pflumio ,  Aride Sirven ,  Anne Dubart

发明人： Pierre Charneau ,  Veronique Zennou ,  Francoise Pflumio ,  Aride Sirven ,  Anne Dubart

IPC分类号： C12N7/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K48/0066 ,  C12N7/00 ,  C12N2740/15043 ,  C12N2740/16042 ,  C12N2740/16111 ,  C12N2740/16211 ,  C12N2740/16311 ,  C12N2830/60

摘要： The present invention provides nucleic acid, vectors, viruses, and recombinant cells comprising triple-stranded structures, such as those resulting from central initiation and termination of HIV-1 reverse transcription at the center of HIV-1 linear DNA genomes. These triplex structures can act as a cis-determinant of HIV-1 DNA nuclear import, allowing infection of non-dividing target cells. In one aspect, the presence of the DNA triplex sequence in an HIV vector strongly stimulates gene transfer in hematopoietic stem cells. The invention also provides methods of using these triplex structures for making recombinant cells, as well as methods of using the recombinant cells to express proteins of interest both in vitro and in vivo.

摘要翻译： 本发明提供了包含三链结构的核酸，载体，病毒和重组细胞，例如由HIV-1线性DNA基因组中心的HIV-1逆转录的中心起始和终止产生的那些。 这些三重结构可以作为HIV-1 DNA核进入的顺式决定簇，允许非分裂靶细胞的感染。 一方面，HIV三聚体序列在HIV载体中的存在强烈刺激造血干细胞中的基因转移。 本发明还提供了使用这些三重结构来制备重组细胞的方法，以及使用重组细胞在体外和体内表达目的蛋白质的方法。

公开(公告)号：US20240229095A1

公开(公告)日：2024-07-11

申请号：US18483460

申请日：2023-10-09

申请人： Progeneer, Inc.

发明人： So Yeon AHN ,  Srivithya VELLAMPATTI KRISHNAMOORTHY ,  Soong Ho UM ,  Sung OH ,  Seung Won SHIN

IPC分类号： C12P21/00 ,  C07K14/005 ,  C07K14/62 ,  C07K16/24 ,  C12N7/00

CPC分类号： C12P21/00 ,  C07K14/005 ,  C07K14/62 ,  C07K16/241 ,  C12N7/00 ,  C12N2740/16051 ,  C12N2740/16311

摘要： This application provides methods and compositions related to constructing nucleic acid hydrogels (e.g., RNA hydrogels) having repetitive monomer units, each monomer unit includes one or more G-quadruplex sequences. These G-quadruplex sequences cross-link the nucleic acid concatemer such that it self-assembles into a hydrogel under appropriate conditions. In some embodiments, each monomeric unit of the nucleic acid concatemer comprises a coding sequence for polypeptide of interest; and the nucleic acid hydrogel formed by the nucleic acid concatemer can be used for expressing the polypeptide in high quantities. In some embodiments, at least two RNA concatemers comprising G-quadruplex sequences are produced, one further comprising a spacer and the other further comprising a sequence encoding a polypeptide of interest. These two RNA concatemers are combined and self assembled to form a single, wideband RNA hydrogel.

公开(公告)号：US20180346928A1

公开(公告)日：2018-12-06

申请号：US16044451

申请日：2018-07-24

申请人： INSTITUT PASTEUR ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

发明人： Pierre CHARNEAU ,  Veronique ZENNOU ,  Francoise PFLUMIO ,  Aude SIRVEN ,  Anne DUBART KUPPERSCHMITT

IPC分类号： C12N15/86 ,  A61K48/00 ,  C12N7/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K48/0066 ,  C12N7/00 ,  C12N2740/15043 ,  C12N2740/16042 ,  C12N2740/16111 ,  C12N2740/16211 ,  C12N2740/16311 ,  C12N2830/60

摘要： The present invention provides nucleic acid, vectors, viruses, and recombinant cells comprising triple-stranded structures, such as those resulting from central initiation and termination of HIV-1 reverse transcription at the center of HIV-1 linear DNA genomes. These triplex structures can act as a cis-determinant of HIV-1 DNA nuclear import, allowing infection of non-dividing target cells. In one aspect, the presence of the DNA triplex sequence in an HIV vector strongly stimulates gene transfer in hematopoietic stem cells. The invention also provides methods of using these triplex structures for making recombinant cells, as well as methods of using the recombinant cells to express proteins of interest both in vitro and in vivo.

公开(公告)号：US20170101652A1

公开(公告)日：2017-04-13

申请号：US15298706

申请日：2016-10-20

申请人： SYMVIVO CORPORATION

发明人： HERBERT ALEXANDER GRAVES ,  Mark Andrew Fox

IPC分类号： C12N15/90 ,  C07K14/46 ,  C07K19/00 ,  C07K14/005

CPC分类号： C12N15/907 ,  C07K14/005 ,  C07K14/463 ,  C07K19/00 ,  C07K2319/02 ,  C07K2319/10 ,  C07K2319/80 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/2402 ,  C12N15/64 ,  C12N15/746 ,  C12N15/902 ,  C12N2740/16031 ,  C12N2740/16311 ,  C12Y302/01055

摘要： There are disclosed hybrid proteins comprising at least one signal sequence; at least one DNA binding domain; and at least one cell penetrating peptide (CPP) domain. In embodiments the CPP domain is a TAT domain, and the DNA binding domain is a HU domain. There is also disclosed the use of the hybrid proteins to introduce exogenous DNA into target cells, and methods for introducing exogenous DNA into target cells using the hybrid proteins.

公开(公告)号：US09241970B2

公开(公告)日：2016-01-26

申请号：US13774053

申请日：2013-02-22

申请人： NoNO Inc.

发明人： Michael Tymianski

IPC分类号： A61K38/00 ,  A61K38/08 ,  A61K38/10 ,  G01N33/68 ,  C07K14/47 ,  A61K45/06 ,  A61K49/00 ,  C07K14/705

CPC分类号： A61K38/162 ,  A61K38/00 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  A61K49/00 ,  C07K14/47 ,  C07K14/70571 ,  C07K2319/10 ,  C12N7/00 ,  C12N2740/16311 ,  C12N2740/16322 ,  C12N2740/16371 ,  G01N33/6893 ,  G01N2800/2871

摘要： The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

摘要翻译： 该应用程序提供来自在经历血管内修复动脉瘤或以其他方式影响CNS的受试者中的PSD-95抑制剂的临床试验的数据。 受试者是否在进行血管内手术之前是否将动脉瘤破裂分层。 如果受试者存活，破裂与更高的死亡率或增加的衰弱有关。 该试验提供证据显示，在进行血管内手术前有和无动脉瘤破裂的受试者。 令人惊讶的是，受病理学和神经认知结果判断的治疗受益最大的受试者是动脉瘤破裂引起蛛网膜下腔出血的受试者。 这些数据构成了PSD-95抑制剂不仅在缺血性和出血性中风中有益，而且对出血或影响CNS，特别是蛛网膜下腔出血的形式有益。

公开(公告)号：US20150232862A1

公开(公告)日：2015-08-20

申请号：US14621308

申请日：2015-02-12

申请人： Symvivo Corporation

发明人： Herbert Alexander Graves ,  Mark Andrew Fox

IPC分类号： C12N15/74

CPC分类号： C12N15/907 ,  C07K14/005 ,  C07K14/463 ,  C07K19/00 ,  C07K2319/02 ,  C07K2319/10 ,  C07K2319/80 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/2402 ,  C12N15/64 ,  C12N15/746 ,  C12N15/902 ,  C12N2740/16031 ,  C12N2740/16311 ,  C12Y302/01055

摘要： There are disclosed nucleic acid vectors for use in both gram positive and gram negative bacteria. In embodiments the vectors comprise a prokaryotic expression cassette and in embodiments comprise a eukaryotic expression cassette. In embodiments the vectors encode a hybrid protein comprising a DNA binding domain, a CPP domain and a signal sequence.

摘要翻译： 公开了用于革兰氏阳性细菌和革兰氏阴性菌的核酸载体。 在实施方案中，载体包含原核表达盒，并且在实施方案中包含真核表达盒。 在实施方案中，载体编码包含DNA结合结构域，CPP结构域和信号序列的杂合蛋白。