JP4987205B2 - 遺伝子送達用核酸製剤および使用方法 - Google Patents
遺伝子送達用核酸製剤および使用方法 Download PDFInfo
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- JP4987205B2 JP4987205B2 JP2001564801A JP2001564801A JP4987205B2 JP 4987205 B2 JP4987205 B2 JP 4987205B2 JP 2001564801 A JP2001564801 A JP 2001564801A JP 2001564801 A JP2001564801 A JP 2001564801A JP 4987205 B2 JP4987205 B2 JP 4987205B2
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| US20040014645A1 (en) * | 2002-05-28 | 2004-01-22 | Advisys, Inc. | Increased delivery of a nucleic acid construct in vivo by the poly-L-glutamate ("PLG") system |
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| TW200403338A (en) * | 2002-07-16 | 2004-03-01 | Advisys Inc | Codon optimized synthetic plasmids |
| WO2004060476A2 (en) * | 2002-12-31 | 2004-07-22 | The Johns Hopkins University | Wound healing method and kits |
| US20040204358A1 (en) * | 2003-01-28 | 2004-10-14 | Advisys, Inc. | Reducing culling in herd animals growth hormone releasing hormone (GHRH) |
| ATE399872T1 (de) * | 2003-03-11 | 2008-07-15 | Serono Lab | Expressionvektoren, die den promotor des ie2-gens des maus cytomegalovirus enthalten |
| CA2521979A1 (en) | 2003-04-09 | 2004-10-28 | University Of Utah Research Foundation | Compositions and methods related to production of erythropoietin |
| TW200424214A (en) * | 2003-04-21 | 2004-11-16 | Advisys Inc | Plasmid mediated GHRH supplementation for renal failures |
| GB0313916D0 (en) | 2003-06-16 | 2003-07-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
| US20090005333A1 (en) * | 2004-01-26 | 2009-01-01 | Vgx Pharmaceuticlas, Inc. | Reducing culling in herd animals growth hormone releasing hormone (ghrh) |
| ES2436741T3 (es) * | 2004-09-22 | 2014-01-07 | St. Jude Children's Research Hospital | Expresión mejorada de Factor IX en vectores de terapia génica |
| US20060094023A1 (en) * | 2004-11-02 | 2006-05-04 | Industrial Technology Research Institute | Method for isolating nucleic acid by using amino surfactants |
| TWI294460B (en) * | 2004-12-23 | 2008-03-11 | Ind Tech Res Inst | Method for stabilizing nucleic acids |
| CN101370927A (zh) * | 2005-12-07 | 2009-02-18 | 基因特伦尼克斯公司 | 可变容积电穿孔室以及其方法 |
| US9037230B2 (en) | 2006-03-03 | 2015-05-19 | Oncosec Medical Incorporated | Method and device for treating microscopic tumors remaining in tissues following surgical resection |
| DK2094086T3 (da) | 2006-11-08 | 2013-11-25 | Veritas Bio LLC | Indgivelse in vivo af dobbeltstrenget rna til en målcelle |
| FR2941152B1 (fr) * | 2009-01-20 | 2013-10-18 | Centre Nat Rech Scient | Vecteurs comprenant une macromolecule anionique et un lipide cationique pour l'administration de petits acides nucleiques. |
| WO2012018594A2 (en) * | 2010-07-26 | 2012-02-09 | Scott & White Healthcare | Plant-derived polysaccharides for delivery of rna-based therapies |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2857499A1 (en) | 2010-10-01 | 2015-04-08 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| CA2831613A1 (en) | 2011-03-31 | 2012-10-04 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| CN104203287B (zh) | 2011-07-12 | 2017-07-14 | 费城健康及教育公司，d/b/a,德雷克塞尔大学医学院 | 新型艰难梭菌dna疫苗 |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| KR20140060541A (ko) | 2011-09-16 | 2014-05-20 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 암을 치료하기 위한 rna 조작된 t 세포 |
| US9708384B2 (en) | 2011-09-22 | 2017-07-18 | The Trustees Of The University Of Pennsylvania | Universal immune receptor expressed by T cells for the targeting of diverse and multiple antigens |
| PT3682905T (pt) | 2011-10-03 | 2022-04-07 | Modernatx Inc | Nucleósidos, nucleótidos e ácidos nucleicos modificados e respetivas utilizações |
| US9272002B2 (en) | 2011-10-28 | 2016-03-01 | The Trustees Of The University Of Pennsylvania | Fully human, anti-mesothelin specific chimeric immune receptor for redirected mesothelin-expressing cell targeting |
| ES2923757T3 (es) | 2011-12-16 | 2022-09-30 | Modernatx Inc | Composiciones de ARNm modificado |
| BR112014020502A2 (pt) | 2012-02-22 | 2019-09-24 | Univ Pennsylvania | sequência de ácido nucleico isolada, receptor quimérico de antígeno isolado, célula, vetor, e, métodos para estimular uma resposta imune, para fornecer uma imunidade antitumoral, para tratamento de um mamífero, para gerar e para expandir uma população de células - t, e para modular a quantidade de citocina secretada por uma célula -t |
| EP2817330B1 (en) | 2012-02-22 | 2020-07-08 | The Trustees of the University of Pennsylvania | Use of icos-based cars to enhance antitumor activity and car persistence |
| WO2013151664A1 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins |
| US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| KR20150029714A (ko) | 2012-07-13 | 2015-03-18 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 이중특이적 항체의 공-도입에 의한 ｃａｒ 세포의 활성 증강 |
| WO2014055442A2 (en) | 2012-10-01 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Compositions and methods for targeting stromal cells for the treatment of cancer |
| US10117896B2 (en) | 2012-10-05 | 2018-11-06 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
| US9598489B2 (en) | 2012-10-05 | 2017-03-21 | The Trustees Of The Univeristy Of Pennsylvania | Human alpha-folate receptor chimeric antigen receptor |
| HUE058785T2 (hu) | 2012-10-08 | 2022-09-28 | Biontech Delivery Tech Gmbh | Karboxilált poliamin-származékok, mint transzfekciós reagensek |
| PT2922554T (pt) | 2012-11-26 | 2022-06-28 | Modernatx Inc | Arn modificado nas porções terminais |
| RS61387B2 (sr) | 2013-02-15 | 2024-06-28 | Bioverativ Therapeutics Inc | Gen optimizovanog faktora viii |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| KR20160067219A (ko) | 2013-10-03 | 2016-06-13 | 모더나 세라퓨틱스, 인코포레이티드 | 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드 |
| WO2015088990A1 (en) | 2013-12-09 | 2015-06-18 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
| EP3097117B1 (en) | 2014-01-21 | 2023-10-04 | Novartis Ag | Enhanced antigen presenting ability of car t cells by co-introduction of costimulatory molecules |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| KR102546296B1 (ko) | 2014-10-31 | 2023-06-21 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 변형된 t 세포에서 유전자 발현의 변경 및 그의 용도 |
| PL3212225T3 (pl) | 2014-10-31 | 2026-03-30 | The Trustees Of The University Of Pennsylvania | Sposoby i kompozycje zmodyfikowanych limfocytów t |
| EP3217989B1 (en) | 2014-10-31 | 2022-01-05 | The Trustees of the University of Pennsylvania | Compositions and methods of stimulating and expanding t cells |
| GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
| AU2015380397B2 (en) | 2015-01-31 | 2021-10-21 | The Trustees Of The University Of Pennsylvania | Compositions and methods for T cell delivery of therapeutic molecules |
| RU2754661C2 (ru) | 2015-05-01 | 2021-09-06 | Дзе Реджентс Оф Дзе Юниверсити Оф Калифорния | Гликанзависимые иммунотерапевтические молекулы |
| WO2017040195A1 (en) | 2015-08-28 | 2017-03-09 | The Trustees Of The University Of Pennsylvania | Methods and compositions for cells expressing a chimeric intracellular signaling molecule |
| KR20180118659A (ko) | 2016-02-01 | 2018-10-31 | 바이오버라티브 테라퓨틱스 인크. | 최적화된 viii 인자 유전자 |
| EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
| US10233419B2 (en) | 2016-06-30 | 2019-03-19 | Zymergen Inc. | Apparatuses and methods for electroporation |
| JP2018035137A (ja) | 2016-07-13 | 2018-03-08 | マブイミューン ダイアグノスティックス エイジーＭａｂｉｍｍｕｎｅ Ｄｉａｇｎｏｓｔｉｃｓ Ａｇ | 新規な抗線維芽細胞活性化タンパク質（ｆａｐ）結合薬剤およびその使用 |
| CN110678190A (zh) | 2017-03-28 | 2020-01-10 | 宾夕法尼亚大学董事会 | 保护移植的组织免受排斥的方法 |
| WO2019129851A1 (en) | 2017-12-29 | 2019-07-04 | Cellectis | Method for improving production of car t cells |
| US11447769B2 (en) | 2018-03-27 | 2022-09-20 | The Trustees Of The University Of Pennsylvania | Modified immune cells having enhanced function and methods for screening for same |
| JP2021524233A (ja) | 2018-05-17 | 2021-09-13 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 薬物耐性免疫細胞及びその用途 |
| WO2020037142A1 (en) | 2018-08-17 | 2020-02-20 | Yale University | Compositions and methods for high-throughput activation screening to boost t cell effector function |
| GB201813528D0 (en) | 2018-08-20 | 2018-10-03 | Ucl Business Plc | Factor IX encoding nucleotides |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| WO2020092455A2 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Car t cell transcriptional atlas |
| US12534714B2 (en) | 2019-03-18 | 2026-01-27 | The Broad Institute, Inc. | Type VII CRISPR proteins and systems |
| TW202042824A (zh) | 2019-03-27 | 2020-12-01 | 賓夕法尼亞大學董事會 | Tn-MUC1嵌合抗原受體（CAR）T細胞療法 |
| JP7803014B2 (ja) | 2019-09-30 | 2026-01-21 | バイオベラティブ セラピューティクス インコーポレイテッド | レンチウイルスベクター製剤 |
| EP4048796B1 (en) | 2019-10-23 | 2025-08-27 | Yale University | Compositions and methods comprising viral vector systems for multiplexed activation of endogenous genes as immunotherapy and viral-based immune-gene therapy |
| JP7859981B2 (ja) | 2020-03-06 | 2026-05-15 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｃｄ４４抗体およびその使用 |
| CA3172447A1 (en) | 2020-03-27 | 2021-09-30 | Erik Hans MANTING | In vivo use of modified cells of leukemic origin for enhancing the efficacy of adoptive cell therapy |
| US12091681B2 (en) | 2020-03-27 | 2024-09-17 | Mendus B.V. | Ex vivo use of modified cells of leukemic origin for enhancing the efficacy of adoptive cell therapy |
| JP2023537565A (ja) | 2020-06-24 | 2023-09-04 | バイオベラティブ セラピューティクス インコーポレイテッド | タンパク質を発現するように改変されたレンチウイルスベクターの調製物から遊離第ｖｉｉｉ因子を除去する方法 |
| WO2022003568A1 (en) | 2020-06-30 | 2022-01-06 | Dcprime B.V. | Use of leukemia-derived cells in ovarian cancer vaccines |
| EP4210832A1 (en) | 2020-09-14 | 2023-07-19 | Vor Biopharma, Inc. | Chimeric antigen receptors for treatment of cancer |
| US20220168407A1 (en) | 2020-11-05 | 2022-06-02 | Dcprime B.V. | Use of tumor-independent antigens in immunotherapies |
| KR20230135075A (ko) | 2021-01-22 | 2023-09-22 | 멘두스 비.브이. | 종양 백신접종 방법 |
| EP4301782A1 (en) | 2021-03-05 | 2024-01-10 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
| WO2022190058A1 (en) | 2021-03-12 | 2022-09-15 | Dcprime B.V. | Methods of vaccination and use of cd47 blockade |
| JP2024531915A (ja) | 2021-08-05 | 2024-09-03 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｍｕｃ抗体およびその使用 |
| WO2023034569A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-cmet antibodies and their uses |
| JP2024534910A (ja) | 2021-09-03 | 2024-09-26 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｌａｍｐ１抗体およびその使用 |
| US20240002800A1 (en) | 2022-05-16 | 2024-01-04 | Mendus B.V. | Use of leukemia-derived cells for enhancing natural killer (nk) cell therapy |
| CN120957741A (zh) | 2023-03-13 | 2025-11-14 | 宾夕法尼亚大学董事会 | 用于肿瘤治疗的car修饰剂的产生 |
| WO2024236547A1 (en) | 2023-05-18 | 2024-11-21 | Inceptor Bio, Llc | Modified phagocytic cells expressing chimeric antigen receptors comprising a herpes virus entry mediator (hvem) co-stimulatory domain and uses thereof |
| WO2025046513A1 (en) | 2023-08-29 | 2025-03-06 | Inceptor Bio, Llc | Methods of manufacturing myeloid-derived cells from hematopoietic stem cells and compositions and uses thereof |
| WO2026047626A1 (en) | 2024-08-30 | 2026-03-05 | Inceptor Bio, Llc | Compositions and methods involving immune cells engineered for binding bispecific antibodies for use in cell therapy |
| CN119925619B (zh) * | 2024-12-31 | 2026-07-14 | 首都医科大学 | 一种递送外源质粒dna的赋形剂及其制备和应用 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4543252A (en) * | 1982-01-21 | 1985-09-24 | The Regents Of The University Of California | Cationic oligopeptides having microbicidal activity |
| JPS60501759A (ja) | 1983-07-01 | 1985-10-17 | バテル メモリアル インステイチユ−ト | 生物分解性ポリペプチド及び薬剤の緩慢な放出のためのその使用 |
| DE3581471D1 (de) | 1984-10-19 | 1991-02-28 | Battelle Memorial Institute | Durch mikroorganismen abbaubares polypeptid und seine verwendung fuer die fortschreitende abgabe von medikamenten. |
| US5749847A (en) * | 1988-01-21 | 1998-05-12 | Massachusetts Institute Of Technology | Delivery of nucleotides into organisms by electroporation |
| JP3368603B2 (ja) | 1992-02-28 | 2003-01-20 | オリンパス光学工業株式会社 | 遺伝子治療用処置具 |
| US5439440A (en) | 1993-04-01 | 1995-08-08 | Genetronics, Inc. | Electroporation system with voltage control feedback for clinical applications |
| AU6714094A (en) | 1993-04-28 | 1994-11-21 | Ribozyme Pharmaceuticals, Inc. | Ocular delivery of nucleic acid |
| US5679647A (en) * | 1993-08-26 | 1997-10-21 | The Regents Of The University Of California | Methods and devices for immunizing a host against tumor-associated antigens through administration of naked polynucleotides which encode tumor-associated antigenic peptides |
| FR2715847B1 (fr) | 1994-02-08 | 1996-04-12 | Rhone Poulenc Rorer Sa | Composition contenant des acides nucléiques, préparation et utilisations. |
| EP0804249A2 (en) | 1994-03-15 | 1997-11-05 | Brown University Research Foundation | Polymeric gene delivery system |
| US6271205B1 (en) * | 1994-09-21 | 2001-08-07 | University Of Massachusetts Medical Center | Cancer treatment by expression of differentiation factor receptor |
| US6040295A (en) * | 1995-01-13 | 2000-03-21 | Genemedicine, Inc. | Formulated nucleic acid compositions and methods of administering the same for gene therapy |
| FR2732218B1 (fr) | 1995-03-28 | 1997-08-01 | Flamel Tech Sa | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s) et leurs procedes de preparation |
| GB9600272D0 (en) * | 1996-01-06 | 1996-03-06 | Univ Nottingham | Polymers |
| US5704908A (en) | 1996-10-10 | 1998-01-06 | Genetronics, Inc. | Electroporation and iontophoresis catheter with porous balloon |
| GB9623051D0 (en) | 1996-11-06 | 1997-01-08 | Schacht Etienne H | Delivery of DNA to target cells in biological systems |
| US6048551A (en) | 1997-03-27 | 2000-04-11 | Hilfinger; John M. | Microsphere encapsulation of gene transfer vectors |
| FR2766706B1 (fr) | 1997-07-30 | 2001-05-25 | Biovector Therapeutics Sa | Complexes particulaires stables de charge globale neutre ou negative de structure multilamellaire composes par au moins une substance biologiquement active globalement anionique et un constituant cationique, leur preparation et utilisation |
| US6040925A (en) | 1997-12-12 | 2000-03-21 | Hewlett-Packard Company | Radial and pruned radial interpolation |
| US6383811B2 (en) | 1997-12-30 | 2002-05-07 | Mirus Corporation | Polyampholytes for delivering polyions to a cell |
| EP2428250A1 (en) * | 1998-07-13 | 2012-03-14 | Genetronics, Inc. | Skin and muscle-targeted gene therapy by pulsed electrical field |
| US7396919B1 (en) * | 1998-07-17 | 2008-07-08 | Mirus Bio Corporation | Charge reversal of polyion complexes |
| US5945290A (en) * | 1998-09-18 | 1999-08-31 | Isis Pharmaceuticals, Inc. | Antisense modulation of RhoA expression |
| FR2786098B1 (fr) * | 1998-11-20 | 2003-05-30 | Flamel Tech Sa | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s), suspension colloidale les comprenant et leurs procedes de fabrication |
| US7005123B1 (en) | 1999-06-17 | 2006-02-28 | Universiteit Gent | Functional poly-α-amino-acid derivatives useful for the modification of biologically active materials and their application |
| AU5624400A (en) | 1999-06-18 | 2001-01-09 | Collaborative Group, Ltd., The | Hyaluronic acid film and matrix for sustained gene transfer |
| WO2001013723A1 (en) | 1999-08-20 | 2001-03-01 | Mirus Corporation | Charge reversal of polyion complexes |
| AU2001241958A1 (en) * | 2000-03-03 | 2001-09-17 | Valentis, Inc. | Improved poloxamer and poloxamine compositions for nucleic acid delivery |
| AU2001296354A1 (en) * | 2000-09-25 | 2002-04-02 | Baylor College Of Medicine | Improved system for regulation of transgene expression |
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2001
- 2001-03-02 WO PCT/US2001/006953 patent/WO2001066149A2/en not_active Ceased
- 2001-03-02 AT AT01918339T patent/ATE511400T1/de not_active IP Right Cessation
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| WO2001066149A3 (en) | 2002-03-14 |
| WO2001066149A2 (en) | 2001-09-13 |
| AU2001245427A1 (en) | 2001-09-17 |
| US20030109478A1 (en) | 2003-06-12 |
| EP1259265B1 (en) | 2011-06-01 |
| JP2003525912A (ja) | 2003-09-02 |
| ATE511400T1 (de) | 2011-06-15 |
| US20070213287A1 (en) | 2007-09-13 |
| EP1259265A2 (en) | 2002-11-27 |
| CA2401327A1 (en) | 2001-09-13 |
| US7491537B2 (en) | 2009-02-17 |
| BR0108962A (pt) | 2002-12-24 |
| DK1259265T3 (da) | 2011-07-11 |
| CA2401327C (en) | 2014-05-06 |
| US7173116B2 (en) | 2007-02-06 |
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