公开(公告)号：US06440743B1

公开(公告)日：2002-08-27

申请号：US09320640

申请日：1999-05-26

申请人： Alexander V. Kabanov ,  Valery Y. Alakov ,  Serguie Vinogradov

发明人： Alexander V. Kabanov ,  Valery Y. Alakov ,  Serguie Vinogradov

IPC分类号： C12N1588

CPC分类号： A61K9/1075 ,  A61K9/5138 ,  A61K9/5146 ,  A61K31/7088 ,  A61K47/58 ,  A61K47/59 ,  A61K47/60 ,  A61K48/00 ,  C08F290/00 ,  C08F297/00 ,  C08L51/003 ,  C08L53/00 ,  C08L71/02 ,  C08L2666/02 ,  C08L2666/24 ,  C08L2666/26

摘要： Compositions for stabilizing polynucleic acids and increasing the ability of polynucleic acids to cross cell membranes and act in the interior of a cell. In one aspect, the invention provides a polynucleotide complex between a polynucleotide and certain polyether block copolymers. The polynucleotide complex can further include a polycationic polymer, as well as suitable targeting molecules and surfactants. The invention also provides a polynucleotide complex between a polynucleotide and a block copolymer comprising a polyether block and a polycation block.

摘要翻译： 用于稳定多核酸并增加多核酸穿过细胞膜并在细胞内部起作用的能力的组合物。 一方面，本发明提供多核苷酸与某些聚醚嵌段共聚物之间的多核苷酸复合物。 多核苷酸复合物还可以包括聚阳离子聚合物，以及合适的靶向分子和表面活性剂。 本发明还提供了多核苷酸与包含聚醚嵌段和聚阳离子嵌段的嵌段共聚物之间的多核苷酸复合物。

公开(公告)号：US06348352B1

公开(公告)日：2002-02-19

申请号：US08403797

申请日：1995-12-04

申请人： H. Michael Shepard ,  Nancy Kan

发明人： H. Michael Shepard ,  Nancy Kan

IPC分类号： C12N1588

CPC分类号： C07K14/4746 ,  A61K38/1709 ,  A61K48/00 ,  C07K14/47 ,  C12N2740/13043

摘要： A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

摘要翻译： 用于转导病理过度增殖的哺乳动物细胞的方法由本发明提供。 该方法需要使细胞与含有编码具有肿瘤抑制功能的基因产物的核酸的合适的逆转录病毒载体接触。 本发明还提供了一种用于治疗由于不存在或存在病理突变的肿瘤抑制基因导致的受试者病理学的方法。

公开(公告)号：US06573101B1

公开(公告)日：2003-06-03

申请号：US09248256

申请日：1999-02-11

申请人： Randal S. Goomer

发明人： Randal S. Goomer

IPC分类号： C12N1588

CPC分类号： C12N15/88

摘要： The present invention relates generally to the delivery of nucleic acid molecules into cells and, more specifically, to compositions and methods for the high efficiency delivery of nucleic acid molecules into cells.

摘要翻译： 本发明一般涉及将核酸分子递送到细胞中，更具体地涉及将核酸分子高效递送到细胞中的组合物和方法。

公开(公告)号：US06372499B1

公开(公告)日：2002-04-16

申请号：US09297519

申请日：1999-05-03

申请人： Patrick Midoux ,  Michel Monsigny

发明人： Patrick Midoux ,  Michel Monsigny

IPC分类号： C12N1588

CPC分类号： C12N15/88 ,  A61K47/645 ,  A61K48/00

摘要： The complex has at least one negatively charged nucleic acid bonded to at least one positively charged polymeric conjugate The conjugate containing a polylysine formed from monomers having free NH3+ groups, and having at least 10% of the free NH3+ groups substituted by residues which can be protonated in a weakly acid medium causing destabilization of cell membranes. Optionally, some of the free NH3+ groups can be substituted by a molecule with a recognition signal by a cell membrane receptor. The free NH3+ groups of the said polylysine make up at least 30% of the monomers of the polymeric conjugate. The residue that causes the destabilization of cell membrane in weak acid of quinolines of the formula: where R1 is hydrogen, R2 is —(CH2)n13 CO2—H, X is hydrogen or chlorine and n is an integer from 1 to 10. The signal is a simple oside or a disaccharide or peptide.

摘要翻译： 所述复合物具有至少一个与至少一个带正电荷的聚合物缀合物连接的带负电荷的核酸。所述缀合物含有由具有游离NH 3 +基团的单体形成的聚赖氨酸，并且具有至少10％的可被质子化的残基取代的游离NH 3 +基团 弱酸介质导致细胞膜的不稳定。可选地，一些游离的NH 3 +基团可以被具有细胞膜受体的识别信号的分子取代。所述聚赖氨酸的游离NH 3+组成至少30％ 导致聚合物缀合物的单体的残留物，其导致下式喹啉的弱酸中细胞膜的不稳定性：其中R1是氢，R2是 - （CH2）n13CO2-H，X是氢或氯，n是整数 信号是一种简单的oside或二糖或肽。

公开(公告)号：US06319715B1

公开(公告)日：2001-11-20

申请号：US09556074

申请日：2000-04-21

申请人： Dan Luo ,  W. Mark Saltzman ,  Ernest Han ,  Nadya Belcheva

发明人： Dan Luo ,  W. Mark Saltzman ,  Ernest Han ,  Nadya Belcheva

IPC分类号： C12N1588

CPC分类号： C12N15/87 ,  Y10S977/906

摘要： The present invention provides a method for enhancing the delivery of nucleic acid molecules to cells by increasing the concentration of cells at the cell surface. The method comprises the step of premixing of nucleic acid:vector molecules with nanoparticles that are biocompatible, reversibly associate with the nucleic acids and have a sedimentation rate which increases the concentration of the nucleic acids at the cell surface so as to enhance delivery into the cells.

摘要翻译： 本发明提供了通过增加细胞表面细胞浓度来增强核酸分子向细胞递送的方法。 该方法包括以下步骤：将核酸：载体分子与生物相容的纳米颗粒预混合，与核酸可逆地结合并具有增加核酸在细胞表面的浓度的沉降速率，从而增强向细胞的传递 。

公开(公告)号：US06794189B2

公开(公告)日：2004-09-21

申请号：US10095682

申请日：2002-05-10

申请人： Jon A. Wolff ,  James E. Hagstrom ,  Vladimir G. Budker ,  Vladimir S. Trubetskoy

发明人： Jon A. Wolff ,  James E. Hagstrom ,  Vladimir G. Budker ,  Vladimir S. Trubetskoy

IPC分类号： C12N1588

CPC分类号： C12N15/88 ,  A61K47/58 ,  A61K47/59 ,  A61K47/60 ,  A61K47/645 ,  A61K48/00 ,  A61K48/0008 ,  A61K48/0025 ,  A61K48/0041 ,  C12N15/87

摘要： An polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.

摘要翻译： 为了向细胞递送核酸，将聚二聚物用于缩合的多核苷酸复合物中。 络合物可以用适量的正电荷和/或负电荷形成，使得所得复合物可以递送到血管外空间并且可以进一步递送至细胞。

公开(公告)号：US06632671B2

公开(公告)日：2003-10-14

申请号：US09796575

申请日：2001-02-28

申请人： Gretchen M. Unger

发明人： Gretchen M. Unger

IPC分类号： C12N1588

CPC分类号： B01J13/08 ,  A61K9/1075 ,  A61K9/5138 ,  A61K9/5161 ,  A61K9/5192 ,  B01J13/02 ,  Y10S977/773 ,  Y10S977/795 ,  Y10S977/897 ,  Y10S977/915 ,  Y10S977/92

摘要： The present invention generally relates to nanocapsules and methods of preparing these nanocapsules. The present invention includes a method of forming a surfactant micelle and dispersing the surfactant micelle into an aqueous composition having a hydrophilic polymer to form a stabilized dispersion of surfactant micelles. The method further includes mechanically forming droplets of the stabilized dispersion of surfactant micelles, precipitating the hydrophilic polymer to form precipitated nanocapsules, incubating the nanocapsules to reduce a diameter of the nanocapsules, and filtering or centrifuging the nanocapsules.

摘要翻译： 本发明一般涉及纳米胶囊和制备这些纳米胶囊的方法。 本发明包括形成表面活性剂胶束并将表面活性剂胶束分散到具有亲水性聚合物的水性组合物中以形成稳定的表面活性剂胶束分散体的方法。 该方法还包括机械地形成稳定的表面活性剂胶束分散体的液滴，沉淀亲水性聚合物以形成沉淀的纳米胶囊，孵育纳米胶囊以减小纳米胶囊的直径，以及过滤或离心纳米胶囊。

公开(公告)号：US06555376B2

公开(公告)日：2003-04-29

申请号：US10201247

申请日：2002-07-24

申请人： Amarnath Maitra ,  Subho Mozumdar ,  Susmita Mitra ,  Indrajit Roy

发明人： Amarnath Maitra ,  Subho Mozumdar ,  Susmita Mitra ,  Indrajit Roy

IPC分类号： C12N1588

CPC分类号： B82Y5/00 ,  A61K47/549 ,  A61K47/6923 ,  A61K47/6929 ,  C12N15/88

摘要： The present invention relates to a process of entrapping genetic materials in nanoparticles of inorganic metal salts of size below 100 nm diameter to form non-viral carriers for delivery of genes. The process comprises the steps of dissolving surfactants and a cosurfactant in oil to obtain reverse micelles. An aqueous solution of genetic material is added to the reverse micelles. Thereafter the reverse micelles are divided into two equal parts. To one part, aqueous solution of inorganic metal salts is dissolved to obtain optically clear and transparent reverse micelles. To the second part aqueous solution of precipitating agent is added to obtain optically clear and transparent reverse micelles. The two equally divided parts of reverse micelles are mixed to form inorganic nanopartcles encapsulating added genetic material. Thereafter, the nanoparticles are separated from reverse micelles, the inorganic nanoparticles are dispersed in water and dialyzed to remove free metal salts, surfactant and oil.

摘要翻译： 本发明涉及一种在大于100nm直径的无机金属盐的纳米颗粒中捕获遗传物质以形成用于递送基因的非病毒载体的方法。 该方法包括将表面活性剂和辅助表面活性剂溶解在油中以获得反胶束的步骤。 将遗传物质的水溶液加入到反胶束中。 此后将反胶束分成两等份。 一方面，将无机金属盐的水溶液溶解，得到透明透明的反胶束。 向第二部分添加沉淀剂水溶液以获得光学透明且透明的反胶束。 将两个等分的部分反胶束混合以形成包封添加的遗传物质的无机纳米颗粒。 此后，将纳米颗粒与反胶束分离，将无机纳米颗粒分散在水中并透析以除去游离金属盐，表面活性剂和油。

公开(公告)号：US06635483B1

公开(公告)日：2003-10-21

申请号：US09382396

申请日：1999-08-25

申请人： Adam Telerman ,  Robert Amson

发明人： Adam Telerman ,  Robert Amson

IPC分类号： C12N1588

CPC分类号： C12N15/113 ,  A61K38/00 ,  C07K14/4711 ,  C07K16/18

摘要： A compound that inhibits the cellular expression of a nucleotide sequence corresponding to all or part of the presenilin 1 gene, the compound comprising an antisense molecule comprising the antisense of a polynucleotide sequence selected from the group consisting of the entire polynucleotide sequence of the presenilin 1 gene, a fragment of the sequence of the presenilin 1 gene, the promoter or other regulatory sequence of the presenilin 1 gene and a polynucleotide sequence that is at least 90% homologous to the polynucleotide sequence of the presenilin 1 gene is described. Pharmaceuticals containing and methods of inhibiting the presenilin 1 gene using such compound are also described. A compound and method of inhibiting the expression product of the presenilin 1 gene also is described. A method of treating a patient having a condition characterized by excessive cell growth also is described. A method of diagnosing cancer also is described. A method of screening drugs that inhibit the presenilin 1 gene also is described. A compound and pharmaceutical that activates the presenilin 1 gene also is described as is a method of treating diseases associated with cell death.

摘要翻译： 抑制对应于早老素1基因全部或部分的核苷酸序列的细胞表达的化合物，所述化合物包含反义分子，所述反义分子包含选自早老素1基因的整个多核苷酸序列的多核苷酸序列的反义 描述了早老素1基因序列的片段，早老素1基因的启动子或其他调控序列以及与早老素1基因的多核苷酸序列至少90％同源的多核苷酸序列。 还描述了含有药物和使用这种化合物抑制早老素1基因的方法。 还描述了抑制早老素1基因表达产物的化合物和方法。 还描述了治疗患有特征在于过度细胞生长的病症的患者的方法。 还描述了诊断癌症的方法。 还描述了筛选抑制早老素1基因的药物的方法。 激活早老素1基因的化合物和药物也被描述为治疗与细胞死亡有关的疾病的方法。

公开(公告)号：US06436708B1

公开(公告)日：2002-08-20

申请号：US09202564

申请日：1999-02-08

申请人： Paola Leone ,  Matthew J. During ,  Frank L. Sorgi

发明人： Paola Leone ,  Matthew J. During ,  Frank L. Sorgi

IPC分类号： C12N1588

CPC分类号： C12N15/86 ,  A61K9/0085 ,  A61K9/1272 ,  A61K47/544 ,  A61K48/00 ,  A61K48/0041 ,  C12N9/88 ,  C12N15/87 ,  C12N15/88 ,  C12N2750/14143

摘要： A gene delivery system which. is both safe and results in long-term expression throughout the brain has been developed. A lipid-entrapped, polycation-condensed DNA (LPD) system has been developed for brain gene delivery, using an adeno-associated vial. (“AAV”) vector in which the transcription unit is flanked by the 145 bp inverted terminal repeats (ITR) of the adeno-associated virus. This AAV plasmid is more effective than a non-ITR containing plasmid in vivo. The results show that the LPD-AAV plasmid complexes efficiently transduce neurons and that gene expression can persist for over 10 months in the brain. Furthermore, the intraventricular delivery method with systemic hyperosmolality results in global gene delivery. The examples show that expression of the human aspartoacyclase (“ASPA”) gene in children with this metabolic disorder can be obtained over a period of many months to a year, with functional activity.

摘要翻译： 一种基因传递系统。 都是安全的，并导致长期表达，整个大脑已经开发出来。 已经开发了用于脑基因递送的脂质包埋的聚阳离子稠合DNA（LPD）系统，使用腺相关小瓶。 （“AAV”）载体，其中转录单位侧翼为腺相关病毒的145bp反向末端重复序列（ITR）。 该AAV质粒在体内比含有非ITR的质粒更有效。 结果表明，LPD-AAV质粒复合物有效转导神经元，并且基因表达可在脑中持续超过10个月。 此外，具有全身高渗性的心室内递送方法导致全球基因递送。 实施例表明，在具有这种代谢紊乱的儿童中，人类天冬酰胺酶（“ASPA”）基因的表达可以在多个月至一年的时间内获得，具有功能活性。