公开(公告)号：US20060099183A1

公开(公告)日：2006-05-11

申请号：US11300722

申请日：2005-12-15

申请人： Pierre Zoldhelyi ,  Janet Cunningham ,  James Willerson

发明人： Pierre Zoldhelyi ,  Janet Cunningham ,  James Willerson

IPC分类号： A61K48/00

CPC分类号： C12N15/86 ,  A61K38/1709 ,  A61K38/36 ,  A61K38/57 ,  A61K48/00 ,  A61K48/0075 ,  C07K14/4713 ,  C07K14/62 ,  C12N2750/14143

摘要： A recombinant adeno-associated virus is used to transduce the cells of a tissue graft ex vivo. More specifically, rAAV encoding a therapeutic protein is delivered to a vascular graft to prevent smooth muscle cell proliferation or thrombosis in the graft. The cells are transfected ex vivo with the recombinant virus carrying a gene known to inhibit the proliferation and migration of vascular smooth muscle cells, thrombosis, and atherosclerosis. The methods can be used for the treatment of restenosis, vascular thrombosis, balloon injury or other vascular pathology.

公开(公告)号：US20050130925A1

公开(公告)日：2005-06-16

申请号：US10972528

申请日：2004-10-25

申请人： Pierre Zoldhelyi ,  Qi Liu ,  George Bobustuc ,  James Willerson

发明人： Pierre Zoldhelyi ,  Qi Liu ,  George Bobustuc ,  James Willerson

IPC分类号： A61K31/202 ,  A61K38/00 ,  A61K48/00 ,  C12N9/02

CPC分类号： C12N9/0083 ,  A61K31/202 ,  A61K38/00 ,  A61K48/00

摘要： Compositions and methods for gene transfer of cyclooxygenase (COX) isoforms alone or in conjunction with administration of one or more fatty acid substrate for the COX isoform (e.g., dihommo-γ-linoleic acid (DGLA)) are disclosed. Methods for enhancing synthesis of the prostaglandins E1 (PGE1) and prostacyclin (PGI2), without marked local production of pro-inflammatory prostaglandin E2 (PGE2) are also disclosed. The compositions and methods are valuable for protection of vascular conduits, kidney function, airway patency, and renal, cardiac, and other allografts, and promoting increased vascular flow, mucus secretion and bicarbonate secretion as protective factors against gastric and duodenal ulcers.

摘要翻译： 公开了单独或与给予一种或多种用于COX同种型的脂肪酸底物（例如二 - γ-亚油酸（DGLA））的环加氧酶（COX）同种型的基因转移的组合物和方法。 用于增强前列腺素E 1（PGE 1）和前列环素（PGI 2 2）的合成的方法，没有明显的局部产生促炎前列腺素 还公开了E 2（PGE 2 2）。 组合物和方法对于保护血管导管，肾功能，气道通畅以及肾，心脏和其他同种异体移植物是有价值的，并且促进增加的血管流动，粘液分泌和碳酸氢盐分泌作为胃和十二指肠溃疡的保护因子。

公开(公告)号：US06214333B1

公开(公告)日：2001-04-10

申请号：US09013366

申请日：1998-01-26

申请人： Pierre Zoldhelyi ,  James T. Willerson

发明人： Pierre Zoldhelyi ,  James T. Willerson

IPC分类号： A61K4800

CPC分类号： C07K14/8114 ,  A61K38/00 ,  A61K48/00 ,  C12N2799/022

摘要： A recombinant adenoviral vector encoding the human tissue factor pathway inhibitor (TFPI) gene is disclosed which is useful for transduction of vascular smooth muscle cells at a selected blood vessel site to provide local vascular expression of TFPI. A method of using the transduced hTFPI cDNA as an in vivo antithrombotic agent to provide localized production of hTFPI for protecting an at-risk site against thrombus deposition is also disclosed. Gene therapy using the new TFPI expression vector is also expected to deter the development of chronic vascular stenosis in blood vessels (arteries, veins, arteriovenous shunts, and endovascular grafts) and deterring intimal hyperplasia.

摘要翻译： 公开了编码人组织因子途径抑制剂（TFPI）基因的重组腺病毒载体，其可用于在选定的血管位点转导血管平滑肌细胞，以提供TFPI的局部血管表达。 还公开了使用转导的hTFPI cDNA作为体内抗血栓形成剂来提供局部生产hTFPI以保护风险部位免受血栓沉积的方法。 使用新的TFPI表达载体的基因治疗也预期将阻止血管（动脉，静脉，动静脉分流和血管内移植物）中慢性血管狭窄的发展并阻止内膜增生。

公开(公告)号：US08617538B2

公开(公告)日：2013-12-31

申请号：US12891406

申请日：2010-09-27

申请人： Pierre Zoldhelyi ,  James T. Willerson ,  Qui Liu ,  Zhi-Qiang Chen

发明人： Pierre Zoldhelyi ,  James T. Willerson ,  Qui Liu ,  Zhi-Qiang Chen

IPC分类号： A61K35/28 ,  C12N5/0789

CPC分类号： C12N5/0663 ,  A61K35/28 ,  C12N5/0692 ,  G01N33/57492 ,  G01N2800/7014

摘要： Compositions containing an effective amount of mesodermal-like multipotent mammalian mononuclear cells that express both CD34 and M-cadherin cell surface markers are used for preventing, treating or reducing the severity of tissue ischemia or an ischemia associated disorder in a mammal. Such uses may include repopulating an in vivo site with new myocytes and/or vascularizing an ischemic or adjacent tissue. Detection of the level and/or distribution of CD34+/M-cadherin+ mesodermal-like precursor cells in a mammalian tissue sample is used to diagnose, among other things, whether transplantation of autologous CD34+/M-cadherin+ mesodermal-like precursor cells to an ischemic site is indicated.

摘要翻译： 用于表达CD34和M-cadherin细胞表面标志物的有效量的中胚层样多能哺乳动物单核细胞的组合物用于预防，治疗或降低哺乳动物中组织缺血或缺血相关病症的严重性。 这种用途可以包括用新的肌细胞重新填充体内位点和/或使缺血或相邻组织血管化。 检测哺乳动物组织样本中CD34 + / M-钙粘蛋白+中胚层样前体细胞的水平和/或分布，用于诊断自体CD34 + / M-钙粘蛋白+中胚层样前体细胞移植到缺血性 站点被指示。

公开(公告)号：US06197756B1

公开(公告)日：2001-03-06

申请号：US09416929

申请日：1999-10-13

申请人： Pierre Zoldhelyi ,  James T. Willerson

发明人： Pierre Zoldhelyi ,  James T. Willerson

IPC分类号： A61K3170

CPC分类号： C07K14/4705 ,  A61K48/00 ,  C12N2799/022

摘要： Methods for induction of E2F-1 related vascular smooth muscle cell (VSMC) death to limit vascular stenosis or restenosis, to regress atherosclerotic plaque and to prevent atherogenesis are disclosed. Also disclosed is an adenovirus vector containing the E2F-1 gene, and a method of transferring the gene to a vessel or graft. A method of limiting cell proliferation and/or reducing cell numbers includes transferring the E2F-1 gene into VSMC to achieve overexpression of E2F-1 gene product, which drives vascular cells into S-phase and thereby causes their subsequent death.

摘要翻译： 公开了诱导E2F-1相关血管平滑肌细胞（VSMC）死亡以限制血管狭窄或再狭窄的方法，回归动脉粥样硬化斑块和预防动脉粥样化形成。 还公开了含有E2F-1基因的腺病毒载体和将基因转移到血管或移植物的方法。 限制细胞增殖和/或减少细胞数量的方法包括将E2F-1基因转移到VSMC中以实现E2F-1基因产物的过度表达，其将血管细胞驱动到S期，从而导致其随后的死亡。