JP2019520814A - 非組み込みウイルス送達系およびその関連方法 - Google Patents
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Abstract
Description
パピローマウイルス
エプスタイン・バーウイルス(EBV)
B型肝炎ウイルス(HBV)
レトロウイルス
ベクター・イン・ベクター系
ベクター・イン・ベクター系の調整可能性
方法
感染性疾患
創傷治癒
別の実施形態では、本開示は、創傷治癒に関連する状態、症候、または副作用を処置、予防、または最小にする方法に関する。開示される組成物は、全身に、または事故、損傷、もしくは外科手術後の創傷に直接投与され得る。外科手術のケースでは、VIV系は、治癒を促進するために予防的に投与され得る。事故、損傷、または外科手術による創傷のケースでは、VIV系は、創傷形成のある程度後に投与され得る。例えば、VIV系は、創傷形成の約1、約2、約3、約4、約5、約10、約12、約24、約36、約48、約60、約72、約84、約96、約108、約120、または約168時間以内に投与され得る。
一実施形態では、本開示は、骨損傷を有する対象を識別するステップ、および治療有効量の本明細書に開示されるウイルス送達系を対象に投与するステップを含む、骨の治癒を増強する方法に関する。ウイルス送達系は、ウイルス担体、異種ウイルスエピソーム複製起点、異種ウイルスエピソーム複製起点に特異的なイニシエータータンパク質をコードする配列、ならびに目的の少なくとも1つの遺伝子、遺伝子産物、shRNA、siRNA、miRNA、および/または他の遺伝子サイレンシングRNAを含み、ここで、ウイルス担体は欠陥のあるインテグラーゼ遺伝子を有し、異種ウイルスエピソームDNA複製起点に特異的なイニシエータータンパク質をコードする配列の発現は、誘導性プロモーターの制御下にある。骨損傷は、事故、損傷、または外科手術によるものであり得、骨の癒合不全または急性骨折または所要の脊椎固定術であり得る。一部の実施形態では、目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、および/または他の遺伝子抑制RNAは、骨形成タンパク質1〜4またはシクロオキシゲナーゼ−2または血管内皮増殖因子またはそれらの断片をコードする。さらに、ある特定の実施形態では、上述の変異体は、骨損傷または関連疾患を処置するために好ましく、またそれらは本開示の範囲内である。
遺伝性遺伝子疾患
P−点突然変異、または全体が1つの遺伝子内にあるあらゆる挿入/欠失
D−1つまたは複数の遺伝子の欠失
C−全染色体の過剰、喪失、またはその両方(染色体異常を参照されたい)
T−トリヌクレオチド反復障害:遺伝子はその長さを伸長している
別の態様では、VIV系は、疾患の治療に使用される細胞または組織を改変するために使用され得る。細胞には、限定はしないが、リンパ球、幹細胞、上皮細胞、神経細胞などの一次細胞が含まれ得る。例えば、VIV系は、がん、感染性疾患、または自己免疫を含む特定疾患に再び向けられるリンパ球を改変するために、かつ遺伝子改変された細胞の長期的存在が健康上のリスクを有する場合に、使用され得る。例えば、VIV系は、高レベルの転写産物因子を要する多能性幹細胞を規定された間隔にわたりプログラムするために、そして組み込まれたウイルスベクターの長期的存在が望ましくない場合に、使用され得る。好適な上皮細胞は、合成皮膚または他の適用に使用され得る上皮細胞を含む。これらは、処置後の正常組織の機能に有害となり本明細書に開示されるVIV系によって最良に送達される栄養因子または増殖因子の、最初の処置の間の発現を要し得る。
開示されるVIV系は、目的の遺伝子または配列の短期、中期、または長期の発現、および開示されるベクターのエピソームでの維持を可能にする。したがって、投薬レジメンは、処置される状態および投与方法に基づいて変化し得る。
本明細書で具体的に定義されない語は、当業者によって理解される意味と同じ意味を有すると理解される。
感染性疾患を処置するためのVIV
この実施例は、感染性疾患を処置するための例示的なVIV構築物を実証する。
実施例2
感染性疾患を予防するためのVIV
実施例3
創傷治癒を増強するためのVIV
実施例4
骨損傷を処置するためのVIV
実施例5
遺伝性疾患を処置するためのVIV
実施例6
カーゴを発現するためのE1を含有するVIV
実施例7
カーゴを発現するためのE1およびE2を含有するVIV
実施例8
カーゴを発現するためのE1およびE2の導入
実施例9
VEGFの発現
実施例10
E1およびE2含有ベクターの開発
3’LTRフォワード CTAATTCACTCCCAACGAAG(配列番号11);および
5’LTRリバース GCCGAGTCCTGCGTCGAGAG(配列番号12)。
実施例11
LCR断片および関連ベクターの開発
実施例12
LCR断片およびE1/E2バリアントを含有するベクターの試験
実施例13
抗体発現
実施例14
マイクロRNA発現およびノックダウン
実施例15
EBVに基づくイニシエータータンパク質
実施例16
最適化されたウイルス送達系を設定するためのLCR断片の選択
実施例17
第1象限下での個体の処置
実施例18
第2象限下での個体の処置
実施例19
第3象限下での個体の処置
実施例20
第4象限下での個体の処置
配列
以下の配列が、本明細書で参照される。
Claims (38)
- a.欠陥のあるインテグラーゼ遺伝子を含有するウイルス担体、
b.異種ウイルスエピソームDNA複製起点、
c.前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも1つのイニシエータータンパク質をコードする配列であって、前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質をコードする配列の発現が誘導性である、配列、および
d.少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNA
を含む、非組み込みウイルス送達系。 - 前記ウイルス担体がレンチウイルスである、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点がパピローマウイルスに由来する、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点がヒトパピローマウイルスまたはウシパピローマウイルスに由来する、請求項3に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点がヒトパピローマウイルス16型(HPV16)に由来する、請求項4に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点がHPV16の長制御領域(LCR)に由来する、請求項5に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点が配列番号1を含む、請求項6に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点が配列番号1の5’トランケーションを含む、請求項6に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点が、配列番号1の少なくとも約200ヌクレオチド、または少なくとも約300ヌクレオチド、または少なくとも約400ヌクレオチド、または少なくとも約500ヌクレオチド、または少なくとも約600ヌクレオチド、または少なくとも約700ヌクレオチドの5’トランケーションを含む、請求項6に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点が、HPV16の前記LCRのFrag1(配列番号2)、Frag2(配列番号3)、Frag3(配列番号4)、またはFrag4(配列番号5)と少なくとも約80%の配列同一性、または少なくとも約85%の配列同一性、または少なくとも約90%の配列同一性、または少なくとも約95%の配列同一性、または少なくとも約98%の配列同一性を含む、請求項6に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点が、HPV16の前記LCRのFrag1(配列番号2)、Frag2(配列番号3)、Frag3(配列番号4)、またはFrag4(配列番号5)を含む、請求項6に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質がE1またはその作動可能な断片を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質がE2またはその作動可能な断片を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質がEBNA−1またはその作動可能な断片を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも2つのイニシエータータンパク質を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも2つのイニシエータータンパク質がE1およびE2またはそれらの作動可能な断片である、請求項15に記載の非組み込みウイルス送達系。
- 前記少なくとも1つのイニシエータータンパク質をコードする配列が単一の別個のプラスミドまたは非組み込みウイルスベクターに存在する、請求項1に記載の非組み込みウイルス送達系。
- 前記系が、前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも2つのイニシエータータンパク質を含み、前記少なくとも2つのイニシエータータンパク質をコードする配列が、単一の別個のプラスミドまたは非組み込みウイルスベクターに存在する、請求項1に記載の非組み込みウイルス送達系。
- 前記系が、前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも2つのイニシエータータンパク質を含み、ここで、第1のイニシエータータンパク質のための配列および第2のイニシエータータンパク質のための配列が、別個のプラスミドまたは非組み込みウイルスベクターに存在する、請求項1に記載の非組み込みウイルス送達系。
- 前記少なくとも1つの遺伝子産物が、抗体、抗体断片、または増殖因子を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記抗体が、抗HER2抗体またはその断片を含む、請求項20に記載の非組み込みウイルス送達系。
- 前記増殖因子が、血管内皮増殖因子(VEGF)またはそのバリアントを含む、請求項20に記載の非組み込みウイルス送達系。
- 前記miRNAが、CCR5 miRNAを含む、請求項1に記載の非組み込みウイルス送達系。
- 請求項1に記載の前記非組み込みウイルス送達系および少なくとも1つの薬学的に許容される担体を含む医薬組成物。
- 少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAを細胞中で発現させる方法であって、
前記細胞を、有効量の非組み込みウイルス送達系に接触させること
を含み、ここで、前記系が、
i.欠陥のあるインテグラーゼ遺伝子を含有するウイルス担体、
ii.異種ウイルスエピソームDNA複製起点、
iii.前記異種ウイルスエピソームDNA複製起点に特異的な少なくとも1つのイニシエータータンパク質をコードする配列であって、前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質をコードする配列の発現が誘導性である、配列、および
iv.少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNA
を含む、方法。 - 少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAを、それを必要とする対象中で発現させる方法であって、
前記対象に、有効量の非組み込みウイルス送達系を投与することを含み、ここで、前記系が、
i.欠陥のあるインテグラーゼ遺伝子を含有するウイルス担体、
ii.異種ウイルスエピソーム複製起点、
iii.異種ウイルスエピソームDNA複製起点に特異的な少なくとも1つのイニシエータータンパク質をコードする配列であって、前記異種ウイルスエピソームDNA複製起点に特異的な前記少なくとも1つのイニシエータータンパク質をコードする配列の発現が誘導性である、配列、および
iv.少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNA
を含む、方法。 - 前記少なくとも1つのイニシエータータンパク質をコードする配列が、単一の別個のプラスミドに存在し、前記少なくとも1つのイニシエータータンパク質が、E1またはE2である、請求項26に記載の方法。
- 前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの第1の発現レベルを開始させるための第1の量の前記単一の別個のプラスミドを、それを必要とする前記対象に投与することをさらに含む、請求項27に記載の方法。
- 前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの第2の発現レベルを開始させるための第2の量の前記単一の別個のプラスミドを、それを必要とする前記対象に投与することをさらに含む、請求項28に記載の方法。
- 前記第2の量が前記第1の量より低いとき、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの発現レベルが減少する、請求項29に記載の方法。
- 前記第2の量が前記第1の量より高いとき、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの発現レベルは増加する、請求項29に記載の方法。
- 前記系が、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの低レベルの基底発現を生じるように最適化されており、ここで、前記異種ウイルスエピソームDNA複製起点が、配列番号1またはHPV16のLCRのFrag1(配列番号2)と少なくとも約80%の配列同一性、または少なくとも約85%の配列同一性、または少なくとも約90%の配列同一性、または少なくとも約95%の配列同一性、または少なくとも約98%の配列同一性を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記系が、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの低レベルの基底発現を生じるように最適化されており、前記異種ウイルスエピソームDNA複製起点が、配列番号1またはHPV16のLCRのFrag1(配列番号2)を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記系が、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの中等度レベルの基底発現を生じるように最適化されており、ここで、前記異種ウイルスエピソームDNA複製起点が、HPV16のLCRのFrag2(配列番号3)、Frag3(配列番号4)、またはFrag4(配列番号5)と少なくとも約80%の配列同一性、または少なくとも約85%の配列同一性、または少なくとも約90%の配列同一性、または少なくとも約95%の配列同一性、または少なくとも約98%の配列同一性を含む、請求項1に記載の非組み込みウイルス送達系。
- 前記系が、前記少なくとも1つの目的の遺伝子、遺伝子産物、shRNA、siRNA、miRNA、または他のRNAの中等度レベルの基底発現を生じるように最適化されており、前記異種ウイルスエピソームDNA複製起点が、HPV16のLCRのFrag2(配列番号3)、Frag3(配列番号4)、またはFrag4(配列番号5)を含む、請求項1に記載の非組み込みウイルス送達系。
- 最適化された非組み込みウイルス送達系を選択する方法であって、
基底発現レベルを選択すること
を含み、ここで、レベルXが選択されるとき、対応するYが選択され、ここでYは、前記非組み込みウイルス送達系に組み入れられるように選択される異種ウイルスエピソームDNA複製起点に対応し、
X=カーゴの基底発現の第1の規定されたレベルの場合、Yは、LCR(配列番号1)またはFrag1(配列番号2)を含み、
X=カーゴの基底発現の第2の規定されたレベルの場合、Yは、HPV16のLCRのFrag2(配列番号3)、Frag3(配列番号4)、またはFrag4(配列番号5)を含む、方法。 - 前記第1の規定されたレベルが、1細胞当たり0.020未満のカーゴのエピソームコピーを含む、請求項36に記載の方法。
- 前記第2の規定されたレベルが、1細胞当たり0.020またはそれよりも高いカーゴのエピソームコピーを含む、請求項36に記載の方法。
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Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100183558A1 (en) | 2008-10-17 | 2010-07-22 | Zhennan Lai | Safe lentiviral vectors for targeted delivery of multiple therapeutic molecules |
US11980663B2 (en) | 2015-07-08 | 2024-05-14 | American Gene Technologies International Inc. | HIV pre-immunization and immunotherapy |
WO2017123918A1 (en) | 2016-01-15 | 2017-07-20 | American Gene Technologies International Inc. | Methods and compositons for the activation of gamma-delta t-cells |
US10137144B2 (en) | 2016-01-15 | 2018-11-27 | American Gene Technologies International Inc. | Methods and compositions for the activation of gamma-delta T-cells |
JP7153332B2 (ja) | 2016-02-08 | 2022-10-14 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | Hivワクチン接種および免疫療法 |
DK3426777T3 (da) | 2016-03-09 | 2022-04-25 | American Gene Tech Int Inc | Kombinationsvektorer og fremgangsmåder til behandling af cancer |
EP3468617A4 (en) | 2016-06-08 | 2020-01-22 | American Gene Technologies International Inc. | INTEGRATED VIRAL ADMINISTRATION SYSTEM AND RELATED METHODS |
EP3481418A4 (en) | 2016-07-08 | 2020-03-11 | American Gene Technologies International Inc. | HIV PRE-IMMUNIZATION AND IMMUNOTHERAPY |
US11583562B2 (en) | 2016-07-21 | 2023-02-21 | American Gene Technologies International Inc. | Viral vectors for treating Parkinson's disease |
CA3057142A1 (en) | 2017-04-03 | 2018-10-11 | American Gene Technologies International Inc. | Compositions and methods for treating phenylketonuria |
AU2021232603A1 (en) * | 2020-03-03 | 2022-10-20 | American Gene Technologies International Inc. | On demand expression of exogenous factors in lymphocytes to treat HIV |
CN112029803A (zh) * | 2020-09-21 | 2020-12-04 | 西人马联合测控(泉州)科技有限公司 | 一种慢病毒过表达病毒载体及其制备方法、用途 |
CN113046330B (zh) * | 2021-03-23 | 2023-03-21 | 中吉智药(南京)生物技术有限公司 | 携带红系基因编辑系统的慢病毒及药物 |
CN114395586A (zh) * | 2022-01-12 | 2022-04-26 | 中国科学院天津工业生物技术研究所 | 非整合慢病毒载体系统在基因编辑器递送中的应用 |
CN114317610A (zh) * | 2022-01-27 | 2022-04-12 | 上海本导基因技术有限公司 | 一种适用于帕金森疾病基因治疗的慢病毒载体 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002506652A (ja) * | 1998-03-20 | 2002-03-05 | トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 組換えアデノ随伴ウイルスのヘルパーを含まない製造のための組成物及び方法 |
US20030013196A1 (en) * | 1999-05-26 | 2003-01-16 | Dana-Farber Cancer Institute, Inc. | Episomally replicating lentiviral vectors |
US6635472B1 (en) * | 1997-08-15 | 2003-10-21 | Rubicon Laboratory, Inc. | Retrovirus and viral vectors |
JP2008518591A (ja) * | 2004-11-02 | 2008-06-05 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | 複製欠損アデノウイルスベクターの製造のためのアデノウイルスアンプリコンおよびプロデューサー細胞、その製造方法および用途 |
JP2012508591A (ja) * | 2008-11-14 | 2012-04-12 | ライフ テクノロジーズ コーポレーション | 細胞を操作するための組成物および方法 |
Family Cites Families (134)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5668255A (en) | 1984-06-07 | 1997-09-16 | Seragen, Inc. | Hybrid molecules having translocation region and cell-binding region |
US5674703A (en) | 1992-12-02 | 1997-10-07 | Woo; Savio L. C. | Episomal vector systems and related methods |
SK282843B6 (sk) | 1993-07-13 | 2002-12-03 | Rhone-Poulenc Rorer S. A. | Defektný rekombinantný adenovírus a farmaceutický prostriedok s jeho obsahom |
WO1999021979A1 (en) * | 1997-10-28 | 1999-05-06 | Maxygen, Inc. | Human papillomavirus vectors |
EP1115290B1 (en) | 1998-10-01 | 2009-03-04 | University of Southern California | Retroviral gene delivery system and methods of use |
US6156514A (en) | 1998-12-03 | 2000-12-05 | Sunol Molecular Corporation | Methods for making recombinant cells |
US6410013B1 (en) | 1999-01-25 | 2002-06-25 | Musc Foundation For Research Development | Viral vectors for use in monitoring HIV drug resistance |
AU2001257611A1 (en) | 2000-04-28 | 2001-11-12 | Avigen, Inc. | Polynucleotides for use in recombinant adeno-associated virus virion production |
US20040214158A1 (en) | 2000-05-12 | 2004-10-28 | Neerja Sethi | Treatment of human papillomavirus (hpv)-infected cells |
AU2001265187A1 (en) | 2000-05-30 | 2001-12-11 | Baylor College Of Medicine | Chimeric viral vectors for gene therapy |
NO314588B1 (no) | 2000-09-04 | 2003-04-14 | Bionor Immuno As | HIV-peptider, antigener, vaksinesammensetning, immunoassay- testsett og en fremgangsmåte for å påvise antistoffer indusert av HIV |
US7122181B2 (en) | 2000-12-19 | 2006-10-17 | Research Development Foundation | Lentiviral vector-mediated gene transfer and uses thereof |
US20030119770A1 (en) | 2001-08-02 | 2003-06-26 | Zhennan Lai | Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors |
AU2002323270A1 (en) | 2001-08-18 | 2003-03-03 | Myriad Genetics, Inc | Composition and method for treating hiv infection |
US7737124B2 (en) | 2001-09-13 | 2010-06-15 | California Institute Of Technology | Method for expression of small antiviral RNA molecules with reduced cytotoxicity within a cell |
US20070203333A1 (en) | 2001-11-30 | 2007-08-30 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
JP2005521393A (ja) | 2002-03-20 | 2005-07-21 | 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 | Hiv治療 |
WO2003093436A2 (en) | 2002-04-30 | 2003-11-13 | University Of Florida | Treatment for phenylketonuria |
US20040161412A1 (en) * | 2002-08-22 | 2004-08-19 | The Cleveland Clinic Foundation | Cell-based VEGF delivery |
AU2003265948B8 (en) | 2002-09-06 | 2009-09-03 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Immunotherapy with in vitro-selected antigen-specific lymphocytes after nonmyeloablative lymphodepleting chemotherapy |
ES2334125T3 (es) | 2002-11-04 | 2010-03-05 | University Of Massachusetts | Interferencia de arn especifico de alelos. |
AU2003283174A1 (en) | 2002-12-11 | 2004-06-30 | Cytos Biotechnology Ag | Method for protein production |
EP1631669A2 (en) | 2003-04-09 | 2006-03-08 | Biodelivery Sciences International, Inc. | Cochleate compositions directed against expression of proteins |
US20060246520A1 (en) | 2003-05-23 | 2006-11-02 | Institut National De La Sante Et De La Recherche Medicale | Gamma delta t cell-mediated therapy |
WO2005005644A1 (en) | 2003-07-11 | 2005-01-20 | Cytos Biotechnology Ag | Gene expression system |
US20050019927A1 (en) | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
US20050138677A1 (en) | 2003-09-16 | 2005-06-23 | Pfister Herbert J. | Transgenic animal model for the treatment of skin tumors |
WO2005028634A2 (en) | 2003-09-18 | 2005-03-31 | Emory University | Improved mva vaccines |
WO2005033282A2 (en) * | 2003-10-01 | 2005-04-14 | Pharmacia & Upjohn Company Llc | Polyamide compositions and therapeutic methods for treatment of human papilloma virus |
US20080039413A1 (en) | 2003-10-21 | 2008-02-14 | Morris David W | Novel compositions and methods in cancer |
EP1753777B1 (en) | 2004-02-25 | 2014-05-07 | Dana-Farber Cancer Institute, Inc. | METHODS AND COMPOSITIONS FOR THE TREATMENT AND PREVENTION OF HIV INFECTION USING TRIM5a |
US20060058255A1 (en) | 2004-03-01 | 2006-03-16 | Jianzhu Chen | RNAi-based therapeutics for allergic rhinitis and asthma |
TWI556829B (zh) * | 2004-04-09 | 2016-11-11 | 艾伯維生物技術有限責任公司 | 用於治療TNFα相關失調症之多重可變劑量療法 |
WO2005118802A2 (en) | 2004-06-03 | 2005-12-15 | The Regents Of The University Of California | Targeting pseudotyped retroviral vectors |
WO2006012221A2 (en) | 2004-06-25 | 2006-02-02 | The Regents Of The University Of California | Target cell-specific short interfering rna and methods of use thereof |
JP4903146B2 (ja) | 2004-08-16 | 2012-03-28 | イミューン ディズィーズ インスティテュート インコーポレイテッド | Rna干渉を送達する方法およびその使用法 |
WO2006039721A2 (en) | 2004-10-08 | 2006-04-13 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases |
EP1647595A1 (en) | 2004-10-15 | 2006-04-19 | Academisch Medisch Centrum bij de Universiteit van Amsterdam | Nucleic acids against viruses, in particular HIV |
US7790446B2 (en) * | 2005-02-11 | 2010-09-07 | Kosagen Cell Factory Oü | Vectors, cell lines and their use in obtaining extended episomal maintenance replication of hybrid plasmids and expression of gene products |
AU2006214278C1 (en) | 2005-02-16 | 2012-07-19 | Miltenyi Biotec Technology, Inc. | Lentiviral vectors and their use |
EP2002003B1 (en) | 2005-05-27 | 2015-12-30 | Ospedale San Raffaele S.r.l. | Gene vector comprising mi-rna |
US20070032443A1 (en) | 2005-08-02 | 2007-02-08 | Jaeseob Kim | Therapy for Alzheimer's disease |
WO2007015122A1 (en) | 2005-08-02 | 2007-02-08 | Genexel, Inc. | Therapy for alzheimer’s disease |
US20070105835A1 (en) | 2005-11-07 | 2007-05-10 | Kazantsev Aleksey G | Compositions and methods for modulating poly(ADP-ribose) polymerase activity |
GB0526211D0 (en) | 2005-12-22 | 2006-02-01 | Oxford Biomedica Ltd | Viral vectors |
WO2007133674A2 (en) | 2006-05-12 | 2007-11-22 | Lentigen Corporation | Lentiviral vector compositions, methods and applications |
WO2007149476A2 (en) | 2006-06-19 | 2007-12-27 | Trustees Of Columbia University In The City Of New York | Assays for non-apoptotic cell death and uses thereof |
US20080003225A1 (en) | 2006-06-29 | 2008-01-03 | Henri Vie | Method for enhancing the antibody-dependent cellular cytotoxicity (ADCC) and uses of T cells expressing CD16 receptors |
US8124752B2 (en) | 2006-07-10 | 2012-02-28 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the MYC gene |
EP1878440A1 (en) | 2006-07-13 | 2008-01-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for increasing the efficiency of therapeutic antibodies using gamma delta cell activator compounds |
BRPI0715112A2 (pt) | 2006-07-26 | 2013-10-01 | Novartis Ag | inibidores de undecaprenil pirofosfato sintase |
US20080199961A1 (en) | 2006-08-25 | 2008-08-21 | Avi Biopharma, Inc. | ANTISENSE COMPOSITION AND METHOD FOR INHIBITION OF miRNA BIOGENESIS |
EP2415783B1 (en) | 2006-10-16 | 2016-12-14 | Genelux Corporation | Modified vaccinia virus strains for use in a diagnostic and therapeutic method |
US8338101B2 (en) | 2007-01-23 | 2012-12-25 | Virco Bvba | Method for designing a drug regime for HIV-infected patients |
AU2008240266A1 (en) | 2007-04-12 | 2008-10-23 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS |
US20080293142A1 (en) | 2007-04-19 | 2008-11-27 | The Board Of Regents For Oklahoma State University | Multiple shRNA Expression Vectors and Methods of Construction |
EP2008656A1 (en) | 2007-06-28 | 2008-12-31 | Bergen Teknologioverforing AS | Compositions for the treatment of hyperphenylalaninemia |
US20110177155A1 (en) | 2007-08-21 | 2011-07-21 | Immune Disease Institute, Inc. | Methods of delivery of agents to leukocytes and endothelial cells |
EP2090659A1 (en) | 2008-02-14 | 2009-08-19 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Infectious particle, process for its preparation and use thereof |
US8288094B2 (en) * | 2008-04-09 | 2012-10-16 | Institut Pasteur | APOBEC3 mediated DNA editing |
GB0810209D0 (en) | 2008-06-04 | 2008-07-09 | Cambridge Entpr Ltd | Pluripotency associated epigenetic factor |
US8629334B2 (en) * | 2008-07-16 | 2014-01-14 | University Of Florida Research Foundation, Inc. | Viral-based transient-expression vector system for trees |
WO2010022195A2 (en) | 2008-08-20 | 2010-02-25 | Virxsys Corporation | Non-integrating lenti/adeno-associated virus hybrid vector system |
WO2010033722A2 (en) | 2008-09-17 | 2010-03-25 | Isogenis, Inc. | Construction of fully-deleted adenovirus-based gene delivery vectors and uses thereof |
US20100183558A1 (en) | 2008-10-17 | 2010-07-22 | Zhennan Lai | Safe lentiviral vectors for targeted delivery of multiple therapeutic molecules |
EP2362783A2 (en) * | 2008-10-31 | 2011-09-07 | Biogen Idec MA Inc. | Light targeting molecules and uses thereof |
WO2010051521A1 (en) | 2008-10-31 | 2010-05-06 | Lentigen Corporation | Cell therapy product for the treatment of hiv infection |
EP2191834A1 (en) | 2008-11-26 | 2010-06-02 | Centre National De La Recherche Scientifique (Cnrs) | Compositions and methods for treating retrovirus infections |
WO2010117974A2 (en) | 2009-04-09 | 2010-10-14 | Stemcyte Inc. | Hiv-resistant stem cells and uses thereof |
BRPI1013771A2 (pt) | 2009-04-13 | 2016-04-05 | Apceth Gmbh & Co Kg | "células-tronco mesenquimais projetadas e método de uso das mesmas para tratar tumores." |
US8728458B2 (en) | 2009-04-30 | 2014-05-20 | The Regents Of The University Of California | Combination anti-HIV vectors, targeting vectors, and methods of use |
DK3329772T3 (da) | 2009-07-15 | 2020-01-27 | Calimmune Inc | Dobbeltvektor til inhibering af human immundefektvirus |
WO2011066578A1 (en) | 2009-11-30 | 2011-06-03 | American Gene Technologies International Inc. | Safe lentiviral vectors for targeted delivery of multiple therapeutic molecules to treat liver cancer |
CN101805750B (zh) | 2009-12-29 | 2011-11-30 | 浙江大学 | 法呢基焦磷酸合成酶rna干扰重组慢病毒载体构建及用途 |
CN102782136A (zh) | 2010-02-18 | 2012-11-14 | 爱默蕾大学 | 表达hiv抗原和gm-csf的载体和用于产生免疫应答的相关方法 |
WO2011119942A1 (en) | 2010-03-25 | 2011-09-29 | Vistagen Therapeutics, Inc. | Induction of ips cells using transient episomal vectors |
US20130090371A1 (en) | 2010-04-20 | 2013-04-11 | President And Fellows Of Harvard College | Methods and compositions for inhibition of beta2-adrenergic receptor degradation |
PL2561078T3 (pl) | 2010-04-23 | 2019-02-28 | Cold Spring Harbor Laboratory | Nowe, strukturalnie zaprojektowane shRNA |
EP2575894B1 (en) | 2010-05-28 | 2015-02-25 | Oxford Biomedica (UK) Ltd | Delivery of lentiviral vectors to the brain |
JP5805089B2 (ja) | 2010-08-10 | 2015-11-04 | タカラバイオ株式会社 | 細胞集団の製造方法 |
EP2625294A4 (en) | 2010-10-07 | 2014-03-26 | Univ Columbia | METHOD OF TREATING CANCER WITH P53 MUTATION |
WO2012061075A2 (en) | 2010-10-25 | 2012-05-10 | The Regents Of The University Of California | Hiv resistant and functional hematopoietic stem/progenitor cells and macrophages from induced pluripotent stem cells |
JP6091435B2 (ja) | 2011-02-22 | 2017-03-08 | カリフォルニア インスティチュート オブ テクノロジー | アデノ随伴ウイルス(aav)ベクターを用いたタンパク質の送達 |
EP2699680B1 (en) | 2011-04-21 | 2017-12-27 | University of Massachusetts | Raav-based compositions and methods for treating alpha-1 anti-trypsin deficiencies |
AU2012340567B2 (en) | 2011-11-22 | 2017-11-23 | The Children's Hospital Of Philadelphia | Virus vectors for highly efficient transgene delivery |
WO2013096455A1 (en) | 2011-12-20 | 2013-06-27 | Dana-Farber Cancer Institute, Inc. | Methods for diagnosing and treating oncogenic kras-associated cancer |
CN104428009A (zh) | 2012-02-07 | 2015-03-18 | 全球生物疗法美国有限公司 | 核酸输送的区室化方法及其组合物和应用 |
WO2013174404A1 (en) | 2012-05-23 | 2013-11-28 | Ganymed Pharmaceuticals Ag | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
KR20150029678A (ko) | 2012-06-06 | 2015-03-18 | 바이오노르 이뮤노 에이에스 | 백신 |
JP2015524264A (ja) * | 2012-07-17 | 2015-08-24 | ユニベルシテ ドゥ ジュネーブ | 遺伝子発現の下方制御のための核酸 |
WO2014052855A1 (en) | 2012-09-27 | 2014-04-03 | Population Diagnostics, Inc. | Methods and compositions for screening and treating developmental disorders |
CN105051192B (zh) | 2012-11-13 | 2020-04-17 | 科迪艾克生物科学公司 | 治疗剂的递送 |
AU2013355327A1 (en) | 2012-12-05 | 2015-06-11 | Sangamo Therapeutics, Inc. | Methods and compositions for regulation of metabolic disorders |
US9642921B2 (en) | 2012-12-20 | 2017-05-09 | Tocagen Inc. | Cancer combination therapy and recombinant vectors |
WO2014117050A2 (en) | 2013-01-26 | 2014-07-31 | Mirimus, Inc. | Modified mirna as a scaffold for shrna |
CN103184224A (zh) | 2013-04-03 | 2013-07-03 | 衡阳师范学院 | 一种抗艾滋病病毒感染的三联miRNA及构建方法 |
US10501803B2 (en) | 2013-05-21 | 2019-12-10 | Max-Planck Gesellschaft zur Förderung der Wissenschaften e.V. | Isoforms of GATA6 and NKX2-1 as markers for diagnosis and therapy of cancer and as targets for anti-cancer therapy |
WO2015017755A1 (en) | 2013-08-02 | 2015-02-05 | The Regents Of The University Of California | Engineering antiviral t cell immunity through stem cells and chimeric antigen receptors |
WO2015042308A2 (en) | 2013-09-18 | 2015-03-26 | City Of Hope | Rna-based hiv inhibitors |
WO2015061491A1 (en) | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Mrna therapy for phenylketonuria |
WO2015070083A1 (en) | 2013-11-07 | 2015-05-14 | Editas Medicine,Inc. | CRISPR-RELATED METHODS AND COMPOSITIONS WITH GOVERNING gRNAS |
EP2878674A1 (en) | 2013-11-28 | 2015-06-03 | Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) | Stable episomes based on non-integrative lentiviral vectors |
GB201322091D0 (en) | 2013-12-13 | 2014-01-29 | Cambridge Entpr Ltd | Modified serpins for the treatment of bleeding disorders |
IL292038A (en) | 2014-04-23 | 2022-06-01 | Juno Therapeutics Inc | Methods for enriching and producing immune cell populations for stress treatment |
BR112016024481A2 (pt) | 2014-04-25 | 2017-10-10 | Bluebird Bio Inc | receptores quiméricos de antígenos com promotor mnd |
WO2015162302A2 (en) | 2014-04-25 | 2015-10-29 | Genethon | Treatment of hyperbilirubinemia |
US20160060707A1 (en) | 2014-08-29 | 2016-03-03 | Immunomedics, Inc. | Identification of Cancer Genes by In-Vivo Fusion of Human Cancer Cells and Animal Cells |
PL3197472T3 (pl) | 2014-09-22 | 2021-12-27 | Tanea Medical Ab | Rekombinowane białka wolne od phe do stosowania w leczeniu fenyloketonurii |
AU2015329696A1 (en) | 2014-10-10 | 2017-04-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods to eliminate cancer stem cells by targeting CD47 |
WO2016061232A2 (en) | 2014-10-14 | 2016-04-21 | Texas Tech University System | Multiplexed shrnas and uses thereof |
WO2016069716A1 (en) | 2014-10-30 | 2016-05-06 | The Scripps Research Institute | Compositions and methods comprising tyrosyl-trna synthetases and resveratrol compounds |
GB201509202D0 (en) | 2015-05-28 | 2015-07-15 | Ge Healthcare Bio Sciences Ab | Semi-static cell culture |
WO2016200997A1 (en) | 2015-06-10 | 2016-12-15 | America Gene Technologies International, Inc. | Non-integrating viral delivery system and methods of use thereof |
US11980663B2 (en) | 2015-07-08 | 2024-05-14 | American Gene Technologies International Inc. | HIV pre-immunization and immunotherapy |
KR102142364B1 (ko) | 2015-08-13 | 2020-08-07 | 베이하오 스템 셀 앤 리제너레이티브 메디슨 리서치 인스티 튜트 씨오.,엘티디. | 유도 연장 만능 줄기 세포, 이의 제조방법 및 사용 방법 |
CN105112370B (zh) | 2015-08-25 | 2019-02-05 | 杭州优善生物科技有限公司 | 一种体外刺激外周血γδT细胞高效增殖的方法及其应用 |
WO2017068077A1 (en) | 2015-10-20 | 2017-04-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Methods and products for genetic engineering |
WO2017100551A1 (en) | 2015-12-09 | 2017-06-15 | Alexion Pharmaceuticals, Inc. | HETEROLOGOUS UTR SEQUENCES FOR ENHANCED mRNA EXPRESSION |
US10137144B2 (en) | 2016-01-15 | 2018-11-27 | American Gene Technologies International Inc. | Methods and compositions for the activation of gamma-delta T-cells |
WO2017123918A1 (en) | 2016-01-15 | 2017-07-20 | American Gene Technologies International Inc. | Methods and compositons for the activation of gamma-delta t-cells |
JP7153332B2 (ja) | 2016-02-08 | 2022-10-14 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | Hivワクチン接種および免疫療法 |
DK3426777T3 (da) | 2016-03-09 | 2022-04-25 | American Gene Tech Int Inc | Kombinationsvektorer og fremgangsmåder til behandling af cancer |
WO2017173453A1 (en) | 2016-04-01 | 2017-10-05 | The Brigham And Women's Hospital, Inc. | Stimuli-responsive nanoparticles for biomedical applications |
EP3468617A4 (en) | 2016-06-08 | 2020-01-22 | American Gene Technologies International Inc. | INTEGRATED VIRAL ADMINISTRATION SYSTEM AND RELATED METHODS |
EP3481418A4 (en) | 2016-07-08 | 2020-03-11 | American Gene Technologies International Inc. | HIV PRE-IMMUNIZATION AND IMMUNOTHERAPY |
US11583562B2 (en) | 2016-07-21 | 2023-02-21 | American Gene Technologies International Inc. | Viral vectors for treating Parkinson's disease |
EP3562494A4 (en) | 2016-12-30 | 2020-08-19 | The Trustees Of The University Of Pennsylvania | GENE THERAPY FOR TREATMENT OF PHENYLKETONURIA |
JP7260170B2 (ja) | 2017-01-09 | 2023-04-18 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | 事前の免疫化ステップのないhiv免疫療法 |
CN110621322A (zh) | 2017-02-08 | 2019-12-27 | 达纳-法伯癌症研究所有限公司 | 用异双功能性化合物进行的可调节的内源性蛋白质降解 |
CA3057142A1 (en) | 2017-04-03 | 2018-10-11 | American Gene Technologies International Inc. | Compositions and methods for treating phenylketonuria |
EP3638779A4 (en) | 2017-06-16 | 2021-03-10 | American Gene Technologies International Inc. | METHODS AND COMPOSITIONS FOR ACTIVATING TUMOR CYTOXICITY VIA HUMAN GAMMA DELTA T CELLS |
AU2018345745A1 (en) | 2017-10-02 | 2020-04-30 | American Gene Technologies International Inc. | Vectors with promoter and enhancer combinations for treating phenylketonuria |
EP3876952A4 (en) | 2018-11-05 | 2022-08-24 | American Gene Technologies International Inc. | VECTOR SYSTEM FOR EXPRESSING REGULATORY RNA |
BR112021024124A2 (pt) | 2019-05-31 | 2022-01-11 | American Gene Tech Int Inc | Expressão otimizada de fenilalanina hidroxilase |
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- 2023-06-27 JP JP2023105190A patent/JP2023120412A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6635472B1 (en) * | 1997-08-15 | 2003-10-21 | Rubicon Laboratory, Inc. | Retrovirus and viral vectors |
JP2002506652A (ja) * | 1998-03-20 | 2002-03-05 | トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 組換えアデノ随伴ウイルスのヘルパーを含まない製造のための組成物及び方法 |
US20030013196A1 (en) * | 1999-05-26 | 2003-01-16 | Dana-Farber Cancer Institute, Inc. | Episomally replicating lentiviral vectors |
JP2008518591A (ja) * | 2004-11-02 | 2008-06-05 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | 複製欠損アデノウイルスベクターの製造のためのアデノウイルスアンプリコンおよびプロデューサー細胞、その製造方法および用途 |
JP2012508591A (ja) * | 2008-11-14 | 2012-04-12 | ライフ テクノロジーズ コーポレーション | 細胞を操作するための組成物および方法 |
Non-Patent Citations (1)
Title |
---|
J. VIROLOGY, 2004年, vol. 78, no. 2, JPN6020011449, pages 658 - 668, ISSN: 0004789751 * |
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KR20230170121A (ko) | 2023-12-18 |
US11976292B2 (en) | 2024-05-07 |
AU2017279542A1 (en) | 2018-12-06 |
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EP3468617A1 (en) | 2019-04-17 |
WO2017213697A1 (en) | 2017-12-14 |
JP2019523767A (ja) | 2019-08-29 |
IL263402A (en) | 2018-12-31 |
CN109641064A (zh) | 2019-04-16 |
EP3468618A2 (en) | 2019-04-17 |
EP3468617A4 (en) | 2020-01-22 |
WO2017214327A3 (en) | 2018-02-15 |
CA3025247A1 (en) | 2017-12-14 |
KR20190023065A (ko) | 2019-03-07 |
JP7173548B2 (ja) | 2022-11-16 |
EP3468618A4 (en) | 2020-01-22 |
US20190264226A1 (en) | 2019-08-29 |
BR112018075399A2 (pt) | 2019-03-19 |
JP2023120412A (ja) | 2023-08-29 |
JP2022191506A (ja) | 2022-12-27 |
KR102609667B1 (ko) | 2023-12-05 |
US20190255190A1 (en) | 2019-08-22 |
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