JP2011523353A - 細胞透過のための過剰に荷電されたタンパク質 - Google Patents
細胞透過のための過剰に荷電されたタンパク質 Download PDFInfo
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| EP3623463B1 (en) | 2013-02-07 | 2021-10-20 | The General Hospital Corporation | Tale transcriptional activators |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| WO2016070129A1 (en) | 2014-10-30 | 2016-05-06 | President And Fellows Of Harvard College | Delivery of negatively charged proteins using cationic lipids |
| WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
| WO2015051214A1 (en) | 2013-10-03 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
| CN111218447B (zh) | 2013-11-07 | 2024-10-11 | 爱迪塔斯医药有限公司 | 使用统治型gRNA的CRISPR相关方法和组合物 |
| CN104127868B (zh) * | 2014-05-06 | 2016-03-02 | 卢戌 | 一种肿瘤疫苗及其应用 |
| JP7061461B2 (ja) * | 2015-02-18 | 2022-04-28 | マサチューセッツ インスティテュート オブ テクノロジー | 水溶性膜貫通タンパク質ならびにその調製および使用方法 |
| EP3337816B1 (en) | 2015-08-20 | 2024-02-14 | Albumedix Ltd | Albumin variants and conjugates |
| CN105219877B (zh) * | 2015-11-06 | 2018-09-25 | 中国医学科学院北京协和医院 | Ccdc59的激动剂在制备骨性关节炎药物中的应用 |
| WO2017120213A1 (en) * | 2016-01-05 | 2017-07-13 | Colorado State University Research Foundation | Compositions comprising resurfaced cell-penetrating nanobodies and methods of use thereof |
| TWI772324B (zh) * | 2016-09-12 | 2022-08-01 | 日商廣津生物化學股份有限公司 | 基於線蟲嗅覺的對氣味物質之趨性行動之評價方法、以及用於該評價方法的培養皿及行動評價系統 |
| EP3679055A1 (en) | 2017-09-08 | 2020-07-15 | The University of Bristol | Protein delivery to membranes |
| GB201902992D0 (en) | 2019-03-06 | 2019-04-17 | Cytoseek Ltd | Product and method |
| US20210023236A1 (en) * | 2019-07-26 | 2021-01-28 | Massachusetts Institute Of Technology | Multi-targeted, tunable, sustained delivery of payloads to charged avascular tissues |
| WO2022226537A2 (en) * | 2021-04-22 | 2022-10-27 | The General Hospital Corporation | Supercharged biovesicles and methods of use thereof |
| CN114452266B (zh) * | 2022-02-09 | 2023-05-19 | 南京凯玛生物科技有限公司 | 一种基于重组核糖体蛋白的核酸药物递送系统及其制备方法和应用 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030134352A1 (en) * | 2002-01-04 | 2003-07-17 | Freimuth Paul I. | Facilitating protein folding and solubility by use of peptide extensions |
| US20030236214A1 (en) * | 1999-06-09 | 2003-12-25 | Wolff Jon A. | Charge reversal of polyion complexes and treatment of peripheral occlusive disease |
| US20040102606A1 (en) * | 2001-04-24 | 2004-05-27 | Danuta Balicki | Histone H2A -derived peptides useful in gene delivery |
| US20070105182A1 (en) * | 2005-11-07 | 2007-05-10 | Raines Ronald T | Cell-permeable green fluorescent protein |
| WO2007143574A1 (en) * | 2006-06-02 | 2007-12-13 | President And Fellows Of Harvard College | Protein surface remodeling |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4270537A (en) * | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| US4596556A (en) * | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4902505A (en) * | 1986-07-30 | 1990-02-20 | Alkermes | Chimeric peptides for neuropeptide delivery through the blood-brain barrier |
| US4886499A (en) * | 1986-12-18 | 1989-12-12 | Hoffmann-La Roche Inc. | Portable injection appliance |
| GB8704027D0 (en) * | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US4790824A (en) * | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US4940460A (en) * | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US4941880A (en) * | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US5339163A (en) * | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| FR2638359A1 (fr) * | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| US5064413A (en) * | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5312335A (en) * | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US6005087A (en) * | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US6399754B1 (en) * | 1991-12-24 | 2002-06-04 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides |
| US5190521A (en) * | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| US5527288A (en) * | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| GB9118204D0 (en) * | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) * | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| US5328483A (en) * | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| US5383851A (en) * | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) * | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) * | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| US5798340A (en) * | 1993-09-17 | 1998-08-25 | Gilead Sciences, Inc. | Nucleotide analogs |
| WO1995024176A1 (en) * | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) * | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| US5596091A (en) * | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5599302A (en) * | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| US5893397A (en) * | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| US5922695A (en) * | 1996-07-26 | 1999-07-13 | Gilead Sciences, Inc. | Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability |
| US6127533A (en) * | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
| US5993412A (en) * | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| US6897297B1 (en) * | 1997-12-03 | 2005-05-24 | Curis, Inc. | Hydrophobically-modified protein compositions and methods |
| US6403779B1 (en) * | 1999-01-08 | 2002-06-11 | Isis Pharmaceuticals, Inc. | Regioselective synthesis of 2′-O-modified nucleosides |
| US8202979B2 (en) * | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
| US20050020525A1 (en) * | 2002-02-20 | 2005-01-27 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| US20050032733A1 (en) * | 2001-05-18 | 2005-02-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA) |
| JP2004528266A (ja) * | 2000-04-12 | 2004-09-16 | インプリクス リミテッド | 薬物送達用組成物 |
| DE60117977D1 (de) * | 2000-06-05 | 2006-05-11 | Boston Scient Ltd | Vorrichtungen zur behandlung von harninkontinenz |
| AU2001287000A1 (en) * | 2000-09-01 | 2002-03-13 | The Center For Blood Research, Inc. | Modified polypeptides stabilized in a desired conformation and methods for producing same |
| US20030175950A1 (en) * | 2001-05-29 | 2003-09-18 | Mcswiggen James A. | RNA interference mediated inhibition of HIV gene expression using short interfering RNA |
| EP2428568B1 (en) * | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Microrna molecules |
| ES2336092T3 (es) * | 2002-01-16 | 2010-04-08 | Genencor International, Inc. | Variantes de proteasas con multiples sustituciones. |
| US7271241B2 (en) * | 2002-04-24 | 2007-09-18 | Los Alamos National Security, Llc | Directed evolution methods for improving polypeptide folding and solubility and superfolder fluorescent proteins generated thereby |
| US9637528B2 (en) * | 2002-04-24 | 2017-05-02 | Los Alamos National Security, Llc | Method of generating ploynucleotides encoding enhanced folding variants |
| US20040092470A1 (en) * | 2002-06-18 | 2004-05-13 | Leonard Sherry A. | Dry powder oligonucleotide formualtion, preparation and its uses |
| JP3996028B2 (ja) * | 2002-09-30 | 2007-10-24 | 株式会社日本触媒 | 蛋白質又はペプチドの細胞内導入方法 |
| CA2513072A1 (en) * | 2003-01-09 | 2004-07-29 | Invitrogen Corporation | Cellular delivery and activation polypeptide-nucleic acid complexes |
| EP1593060A2 (en) * | 2003-01-21 | 2005-11-09 | The Trustees Of The University Of Pennsylvania | Computational design of a water-soluble analog of a protein, such as phospholamban and potassium channel kcsa |
| US20040162235A1 (en) * | 2003-02-18 | 2004-08-19 | Trubetskoy Vladimir S. | Delivery of siRNA to cells using polyampholytes |
| EP1954713B1 (en) * | 2005-11-04 | 2012-11-14 | Evrogen, JSC | Modified green fluorescent proteins and methods for using same |
| WO2008054544A2 (en) * | 2006-05-22 | 2008-05-08 | Immune Disease Institute, Inc. | Method for delivery across the blood brain barrier |
| US9221886B2 (en) * | 2009-04-28 | 2015-12-29 | President And Fellows Of Harvard College | Supercharged proteins for cell penetration |
-
2009
- 2009-04-28 JP JP2011507588A patent/JP2011523353A/ja active Pending
- 2009-04-28 EP EP09739610A patent/EP2297182A4/en not_active Withdrawn
- 2009-04-28 AU AU2009243187A patent/AU2009243187C1/en not_active Ceased
- 2009-04-28 CN CN200980123772.1A patent/CN102066405B/zh not_active Expired - Fee Related
- 2009-04-28 WO PCT/US2009/041984 patent/WO2009134808A2/en not_active Ceased
- 2009-04-28 CA CA2725601A patent/CA2725601A1/en not_active Abandoned
- 2009-04-28 US US12/989,829 patent/US20110112040A1/en not_active Abandoned
-
2014
- 2014-06-03 JP JP2014114885A patent/JP2014159484A/ja active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030236214A1 (en) * | 1999-06-09 | 2003-12-25 | Wolff Jon A. | Charge reversal of polyion complexes and treatment of peripheral occlusive disease |
| US20040102606A1 (en) * | 2001-04-24 | 2004-05-27 | Danuta Balicki | Histone H2A -derived peptides useful in gene delivery |
| US20030134352A1 (en) * | 2002-01-04 | 2003-07-17 | Freimuth Paul I. | Facilitating protein folding and solubility by use of peptide extensions |
| US20070105182A1 (en) * | 2005-11-07 | 2007-05-10 | Raines Ronald T | Cell-permeable green fluorescent protein |
| WO2007143574A1 (en) * | 2006-06-02 | 2007-12-13 | President And Fellows Of Harvard College | Protein surface remodeling |
Non-Patent Citations (6)
| Title |
|---|
| JPN6015002267; ＣＭＬＳ， Ｃｅｌｌ Ｍｏｌ． Ｌｉｆｅ Ｓｃｉ． ｖｏｌ．６２, 2005, ｐｐ．１８３９-１８４９ * |
| JPN6015002268; ＭＯＬＥＣＵＬＡＲ ＴＨＥＲＡＰＹ ｖｏｌ．５ ｎｏ．２, 2002, ｐｐ．１０４-１１４ * |
| JPN6015002269; Ｂｉｏｃｈｅｍｉｓｔｒｙ ｖｏｌ．３６, 1997, ｐｐ．３００８-３０１７ * |
| JPN6015002271; Ｂｉｏｃｈｅｍｉｃａｌ ａｎｄ Ｂｉｏｐｈｙｓｉｃａｌ Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ ｖｏｌ．２９１, 2002, ｐｐ．３６７-３７１ * |
| JPN6015002272; ＴＨＥ ＪＯＵＲＮＡＬ ＯＦ ＢＩＯＬＯＧＩＣＡＬ ＣＨＥＭＩＳＴＲＹ ｖｏｌ．２７５ ｎｏ．４３, 2000, ｐｐ．３３２１３-３３２２１ * |
| JPN6015002274; ＪＯＵＲＮＡＬ ＯＦ ＶＩＲＯＬＯＧＹ ｖｏｌ．７９ ｎｏ．１９, 2005, ｐｐ．１２１８５-１２１９８ * |
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2009243187B2 (en) | 2015-09-17 |
| WO2009134808A2 (en) | 2009-11-05 |
| JP2014159484A (ja) | 2014-09-04 |
| AU2009243187B9 (en) | 2015-11-12 |
| US20110112040A1 (en) | 2011-05-12 |
| EP2297182A2 (en) | 2011-03-23 |
| CA2725601A1 (en) | 2009-11-05 |
| AU2009243187C1 (en) | 2015-12-24 |
| AU2009243187A1 (en) | 2009-11-05 |
| CN102066405A (zh) | 2011-05-18 |
| EP2297182A4 (en) | 2012-08-15 |
| WO2009134808A3 (en) | 2010-06-10 |
| CN102066405B (zh) | 2015-09-30 |
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