JP2012510812A - 亜鉛フィンガーヌクレアーゼを使用したラットのゲノム編集 - Google Patents
亜鉛フィンガーヌクレアーゼを使用したラットのゲノム編集 Download PDFInfo
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Abstract
Description
本明細書に開示する、方法の実践、ならびに組成物の調製および使用は、別段の指示がない限り、当該分野の技術範囲内である、分子生物学、生化学、クロマチン構造および分析、計算化学、細胞培養、組換えDNA、ならびに関連分野における従来の技術を用いる。これらの技術は、文献に完全に説明されている。例えば、Sambrook et al.MOLECULAR CLONING:A LABORATORY MANUAL,Second edition,Cold Spring Harbor Laboratory Press,1989 and Third edition,2001、Ausubel et al.,CURRENT PROTOCOLS IN MOLECULAR BIOLOGY,John Wiley&Sons,New York,1987および定期改訂、the series METHODS IN ENZYMOLOGY,Academic Press,San Diego、Wolffe,CHROMATIN STRUCTURE AND FUNCTION,Third edition,Academic Press,San Diego,1998、METHODS IN ENZYMOLOGY,Vol.304,「Chromatin」(P.M.Wassarman and A.P.Wolfee,eds.),Academic Press,San Diego,1999、およびMETHODS IN MOLECULAR BIOLOGY,Vol.119,「Chromatin Protocols」(P.B.Becker,ed)Humana Press,Totowa,1999を参照されたい。
「核酸」、「ポリヌクレオチド」、および「オリゴヌクレオチド」という用語は、互換的に使用され、線状または環状配座であり、一本鎖または二本鎖形態のいずれかである、デオキシリボヌクレオチドまたはリボヌクレオチドポリマーを指す。本開示については、これらの用語は、ポリマーの長さに関して制限するものとして解釈されるものではない。用語は、天然ヌクレオチドの公知の類似体、ならびに塩基部分、糖部分、および/またはリン酸部分において修飾されるヌクレオチド(例えば、ホスホロチエート骨格)を包含する。一般に、特定ヌクレオチドの類似体は、同一の塩基対合特異性を有する、すなわち、Aの類似体は、Tと塩基対合する。
1つもしくは複数のラット遺伝子のゲノム編集(例えば、開裂、変異、不活性化、および/またはランダム変異)のために使用することができる、亜鉛フィンガーヌクレアーゼ(ZFN)を本明細書に説明する。ZFNは、亜鉛フィンガータンパク質(ZFP)およびヌクレアーゼ(開裂)ドメイン(例えば、開裂ハーフドメイン)を含む。
亜鉛フィンガー結合ドメインは、選択される配列に結合するように改変することができる。例えば、Beerli et al.(2002)Nature Biotechnol.20:135〜141、Pabo et al.(2001)Ann.Rev.Biochem.70:313〜340、Isalan et al.(2001)Nature Biotechnol.19:656〜660、Segal et al.(2001)Curr.Opin.Biotechnol.12:632〜637、Choo et al.(2000)Curr.Opin.Struct.Biol.10:411〜416を参照されたい。改変された亜鉛フィンガー結合ドメインは、天然に存在する亜鉛フィンガータンパク質と比較して、新規結合特異性を有することができる。改変方法は、合理的設計および種々の種類の選択を含むが、それらに限定されない。合理的設計は、例えば、三重項(または四重項)ヌクレオチド配列、および個々の亜鉛フィンガーアミノ酸配列を含むデータベースを使用することを含み、各三重項または四重項ヌクレオチド配列は、特定の三重項または四重項配列を結合する、亜鉛フィンガーの1つもしくは複数のアミノ酸配列と会合する。例えば、参照することによってその全体が組み込まれる、共同所有の米国特許第6,453,242号および6,534,261号を参照されたい。
ZFNはまた、ヌクレアーゼ(開裂ドメイン、開裂ハーフドメイン)を含む。本明細書に開示する、融合タンパク質の開裂ドメイン部分は、任意のエンドヌクレアーゼまたはエキソヌクレアーゼから取得することができる。開裂ドメインがそこから得ることができる例示的エンドヌクレアーゼは、制限エンドヌクレアーゼ、ホーミングエンドヌクレアーゼを含むが、それらに限定されない。例えば、2002−2003 Catalogue,New England Biolabs,Beverly,MA、およびBelfort et al.(1997)Nucleic Acids.Res.25:3379〜3388を参照されたい。DNAを開裂する付加的な酵素は、公知である(例えば、S1ヌクレアーゼ、マングビーンヌクレアーゼ、膵DNase I、ミクロコッカスヌクレアーゼ、酵母菌HOエンドヌクレアーゼ、Linn et al.(eds)Nucleases,Cold Spring Harbor Laboratory Press,1993も参照)。これらの酵素(またはその機能的断片)のうちの1つもしくは複数は、開裂ドメインおよび開裂ハーフドメインの源として使用することができる。
任意のラット遺伝子内に標的部位を有する任意のヌクレアーゼは、本明細書に開示する方法に使用することができる。例えば、ホーミングエンドヌクレアーゼおよびメガヌクレアーゼは、非常に長い認識配列を有し、そのうちのいくつかは、統計的基礎において、ヒトサイズのゲノム内に一度存在する可能性が高い。ラット遺伝子内に標的部位を有する任意のそのようなヌクレアーゼは、ラット遺伝子内の標的開裂のために、亜鉛フィンガーヌクレアーゼの代わりに、またはそれに加えて、使用することができる。
本明細書に説明するZFNは、例えば、ZFN mRNAの注入を含む、任意の好適な手段によって、標的ラット細胞に送達し得る。Hammerschmidt et al.(1999)Methods Cell Biol.59:87〜115を参照されたい。
開示した方法および組成物は、任意のラット遺伝子または複数の遺伝子のゲノム編集のために使用することができる。ある用途では、方法および組成物は、ラットゲノム配列の不活性化のために使用することができる。別の用途では、方法および組成物は、未編集遺伝子またはヒト化ラット遺伝子の組み込みと比較して、異なる発現を有する遺伝子の新規対立形質の生成を含むランダム変異の生成を可能にし、順に、動物モデルの生成を可能にする。他の用途では、方法および組成物は、これらの遺伝子の新規対立形質を持つ動物の特定または選択を可能にする、遺伝子の画定された位置においてランダム変異を作製するために使用することができる。別の用途では、方法および組成物は、ラットゲノムの任意の選択した領域内への外因性(ドナー)配列の標的組み込みを可能にする。調節配列(例えば、プロモータ)は、対象部位において、標的とした方法で組み込むことができる。「組み込み」とは、物理的挿入(宿主細胞のゲノム内)および、加えて、核酸複製過程を介する宿主細胞ゲノム内へのドナー配列のコピーによる組み込みの両方を意味する。ドナー配列はまた、shRNA、miRNA等の核酸を含むことができる。
実施例1:ZFNは、ラットC6細胞において標的破壊を誘発する
実質的に、Urnov et al.(2005)Nature435(7042):646〜651に説明するように、ラットp53を標的としたZFNを設計し、プラスミド内に組み込んだ。代表的なラットp53設計のための認識へリックスを下記の表1に示す。これらのZFNのための標的部位を表2に示す。
代表的なGFP亜鉛フィンガー設計のための認識ヘリックスを下記の表3に示す。
実施例1に説明する、GFP特異性ZFNをまた、さまざまな濃度で、前核注入(PNI)または(ZFN mRNAの)細胞質注入によって、Michalkiewicz et al.(2007)J.Amer.Phys.Society 293:H881−H894に説明される、GFPを発現するトランスジェニックラットから取得した1つの細胞胚内に導入した(図3を参照)。
下記に説明するように、ZFNを、内因性遺伝子座を開裂するように設計した。
1つの実験では、上記に説明するように、ZFNを、内因性ラットIgM遺伝子を開裂するように設計し、ラットC6細胞中の開裂活性を試験した。例示的ラットIgM標的ZFPを下記の表6に示す。
断片A、B:Surveyor(商標)ヌクレアーゼ開裂産物の期待寸法
ヒット:正確なSurveyor(商標)ヌクレアーゼ開裂産物を示すラット
ZFNもまた、ラットの内因性Rab38遺伝子座、特に、ラットRab38遺伝子のエクソン1を標的とするように設計した。例示的なRab38亜鉛フィンガー設計を下記の表8に示す。
実施例3に説明する、IgM修飾ラット#19、#46、および#8を野生型ラットと交配させ、尾部生体検査を実施し、ゲノムDNAを単離し、次いで、CEL−IおよびPCRアッセイを、子ラットから精製された核酸上で実施した。
標的ZFN誘発二本鎖切断後の2つのDNA修復結果の可能性が存在する(図12)。切断は、塩基欠失または追加を含む、変異につながる、非相同末端連結(NHEJ)によって修復され得るか、または、ドナーDNAの存在下で、ドナーDNAは、相同組換え(HR)による二本鎖切断を修復するためのテンプレートとして使用することができる。ドナーDNAが、特異的配列変化をコードする場合には、これらの故意の変異は、標的部位において、有機体のゲノム中に組み込まれる。
プラスミドもまた、ラットゲノムのrRosa26核酸領域内へのNotIおよびPmeI RFLP部位の組込みを標的とするように構築した。プラスミドの設計および構築は、上記の実施例5に説明するとおりであった。相同性rRosa26領域を増幅するために使用したPCRプライマー対を表14に説明する。
プラスミドを、マウスゲノムのmMdr1a核酸領域、またはラットゲノムのrMdr1a核酸領域内へのNotIおよびPmeI RFLP部位の組込みを標的とするために構築した。プラスミドの設計および構築は、上記の実施例5に説明するとおりであった。相同性Mdr1a領域を増幅するために使用したPCRプライマー対を表15および16に説明する。「m」は、マウスを表し、「r」は、ラットを表す。
RFLPよりも大きい核酸断片の標的組込みを試験するために、コンストラクトを、ラットのPXRおよびrRosa26核酸ゲノム領域、およびマウスのmMdr1a核酸ゲノム領域内へのGFP発現カセットの標的組込みのために設計し、調製した。簡潔に言うと、ヒトPGKプロモータ、GFPオープンリーディングフレーム、およびポリアデニル化信号を含む、GFP発現カセットを、以下のプライマー(PGKGFP−F−NotI(5′−aaagcggccgcttggggttgcgccttttcc)(配列番号164)およびPGKGFP−R NotI(5′−aaaagcggccgccatagagcccaccgcatc)(配列番号165))を使用して、端部においてNotI制限部位を導入するために(図14)、PCRを使用して増幅した。次いで、PCR断片を、実施例5〜7において構築したNotI含有プラスミドへクローン化した。
Sigma社のウェブサイトに説明されるように、一対の亜鉛フィンガーヌクレアーゼを各標的組込み部位のために設計し、クローン化した。さらなる情報は、参照することによって本明細書に組み込まれる、Science(2009)325:433を参照されたい。次いで、まず、37℃で2時間の間、10μLの緩衝液2(NEB、#B7002S)、10μLの10XのBSA(100XのBSAから希釈、NEB、#B9001S)、8μLのXbaI(NEB、#R0145S)を含む、100μLの反応物中の20μgの各マキシプレップされたZFN発現プラスミドDNAを消化させることによって、ZFN発現mRNAをインビトロで産生した。反応物を、100μLのフェノール/クロロホルム(Sigma、P2069)で抽出し、10分間、20,000Xgにわたって遠心分離した。水性上清を、10μLの3M NaOAc(Sigma、S7899)および250μLの100%エタノールで沈殿させ、25分間、室温で、最高速度で遠心分離した。得られた沈殿物を、0.02μMのフィルターを介してろ過した、300μLの70%エタノールを追加することによって洗浄した。沈殿物を乾燥させ、20μLの0.02μMでろ過された0.1xTE中で再懸濁した。
ラットまたはマウスゲノム中に核酸を組み込むために、亜鉛フィンガーヌクレアーゼmRNAを、0.02umのフィルターでろ過した、マキシプレップされた標的DNAで混合した。核酸混合物は、1部のZFN mRNAから一部のドナーDNAを含んだ。次いで、公知の方法を使用して、核酸混合物を単細胞胚前核中に微量注入した。注入された胚を、インビトロで培養するか、または偽母親に移動させた。一回に生産された動物の得られた胚/胎児、または足指/尾を、DNA抽出および分析のために採取した。
組織から抽出された標的核酸を増幅するためのPCR条件を、実施例10に説明するように、抽出された1〜64の細胞を有する胚を使用して試験した。50μLの反応物中の最大5μLのEpicenterのQuickExtract溶液を含む、反応物中での60℃で4分間のエクステンションを有する、36増幅サイクルを使用して、マウスmMdr1a標的領域を含む、900bp断片を増幅した(図16)。これらの結果は、QuickExtractがPCR増幅に干渉せず、DNAが 1〜10個の細胞のみから抽出されたサンプルから増幅することができることを示す。感度を向上するために、PCRサイクルの数を増加し得るか、またはネスト化されたPCR反応を実施し得る。
上述のように、ラットゲノムのPXR領域内へNotI RFLP部位を組み込むためのドナープラスミド(800bpのアームを有する)を、ZFN mRNAを有するラット胚中に注入した。多くの胚から抽出されたDNAを使用して、PCR後に、NotI制限酵素分析、およびCel−Iエンドヌクレアーゼ分析を実施した。PCR増幅は、多くの胚で成功し(図17A)、Cel−Iエンドヌクレアーゼ分析は、断片の大半が、所望の標的において核酸配列変化を有したことを明らかにした(図17B)。
実施例8に説明するように、マウスmMdr1a領域へのNotI RFLPの標的組込みを反復した。mMdr1a領域を、PCRを使用して増幅し、NotIで消化した。PCR増幅は、多くの胚で成功し(図18)、NotIでの消化は、多くの胚が組み込まれたRFLP部位を含んだことを明らかにした(例えば、列13、17、19、20、および23を参照)。全部で、32個の胚のうちの7個において標的組込みが発生した。
感度レベルを判定するために、胚盤胞からのPXR領域のPCR増幅を試験した。PCR反応物は、50μLの反応物に対して、5μLのテンプレート、5μLのPCR緩衝液、5μLの各プライマー、0.5μLのTaqポリメラーゼ酵素、および33.5μLの水を含んだ。テンプレートは、ラット胚盤胞から抽出された不希釈DNA、または1:2、1:6、1:10、および1:30の比率で希釈されたDNAを含んだ(図20)。
上述のように、ラットゲノムのPXR領域へNotI RFLP部位を組み込むためのドナープラスミド(800bpの相同性アームを有する)を、ZFN mRNAを有するラット胚中に注入した。合計123個の胚を注入し、106個が生存した。毒性を試験するために、減少した濃度の核酸を注入した。2日目に、5ngの核酸を注入された51個の胚のうちの17個が生存し、2細胞期胚に分割した。2日目に、2ngの核酸を注入された23個の胚のうちの14個が生存し、2細胞期胚に分割した。2日目に、10ngの核酸を注入された29個の胚のうちの12個が生存し、2細胞期胚に分割した。2日目に、10個の未注入の対照胚のうちのすべてが生存し、2細胞期胚に分割した。
上述のように、マウスゲノムのmMdr1a領域にNotIを導入するためのドナープラスミド(800bpの相同性アームを有する)を、ZFN mRNAを有するマウス胚中に注入した。12.5dpcにおいて、4匹の十分に発達した胎児のうちの1匹は、NotI部位に対して陽性であった。すべての4つの脱落膜は、陰性であった(図22)。
上述のように、マウスゲノムのmMdr1a領域にGFPカセットを導入するためのドナープラスミド(800bpの相同性アームを有する)を、ZFN mRNAを有するマウス胚中に注入した。12.5dpcにおいて、40匹の胎児のうちの2匹は、GFPカセットに対して陽性であった(図23)。
上述のように、ラットゲノムのPXR領域にNotIを導入するためのドナープラスミド(800bpの相同性アームを有する)を、ZFN mRNAを有するマウス胚中に注入した。13dpcにおいて、8匹の胎児のうちの1匹は、NotI部位に対して陽性であった(図24)。
Claims (12)
- ラット細胞の1つもしくは複数の内因性細胞遺伝子を修飾するための方法であって、
1つもしくは複数の亜鉛フィンガーヌクレアーゼ(ZFN)が発現し、かつ前記1つもしくは複数の内因性細胞遺伝子が開裂し、修飾されるような条件下で、前記1つもしくは複数の遺伝子内の標的部位に結合する、1つもしくは複数のZFNをコードする、1つもしくは複数のポリヌクレオチドを前記ラット細胞内に導入すること、
を含む、方法。 - 前記修飾は、前記1つもしくは複数の内因性細胞遺伝子の開裂によって刺激された相同組換えによって、外因性配列をラット細胞のゲノム内に導入することを含む、請求項1に記載の方法。
- 前記外因性配列は、前記ゲノム内に物理的に組み込まれる、請求項2に記載の方法。
- 前記外因性配列は、核酸複製過程を介して、宿主細胞ゲノムへの前記外因性配列のコピーによって、前記ゲノム内に組み込まれる、請求項2に記載の方法。
- 前記核酸複製過程は、二本鎖切断の相同指向修復を含む、請求項4に記載の方法。
- 前記核酸複製過程は、非相同依存性標的組み込みを含む、請求項4に記載の方法。
- 前記修飾は、開裂後の非相同末端連結から生じる、請求項1に記載の方法。
- 第1および第2の亜鉛フィンガーヌクレアーゼは、2つの部位において前記ゲノムを開裂し、さらに、前記非相同末端連結は、前記第1の開裂部位と第2の開裂部位との間に欠失をもたらす、請求項7に記載の方法。
- 前記亜鉛フィンガーヌクレアーゼは、IIS型制限エンドヌクレアーゼの開裂ドメインまたは開裂ハーフドメインを含む、請求項1〜8のうちのいずれか一項に記載の方法。
- ラットの1つもしくは複数の標的遺伝子の生殖細胞系列の破壊のための方法であって、前記方法は、ラット胚の1つもしくは複数の細胞のゲノム内の1つもしくは複数の遺伝子配列を修飾することを含み、
請求項1〜9のうちのいずれか一項に記載の方法に従い、ラット胚の1つもしくは複数の細胞内の前記標的遺伝子のうちの1つもしくは複数を修飾することと、
前記ラット胚を発達させることと、を含み、前記修飾された遺伝子配列が、前記性成熟ラットの配偶子の少なくとも一部分内に存在する、
方法。 - 対象のラット遺伝子座に1つもしくは複数の遺伝性変異対立遺伝子を作製する方法であって、
請求項1〜9のうちのいずれか一項に記載の方法によって、ラット胚の1つもしくは複数の細胞のゲノム内の1つもしくは複数の遺伝子座を修飾することと、
前記ラット胚を性成熟期に成長させることと、
前記性成熟ラットが子孫を産生させることと、を含み、前記子孫のうちの少なくとも数匹は、前記変異対立遺伝子を含む、
方法。 - 請求項1〜11のうちのいずれか一項に記載の方法によって産生された、1つもしくは複数の修飾された対立遺伝子を含む、ラット。
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---|---|---|---|---|
JP2016500262A (ja) * | 2012-12-12 | 2016-01-12 | ザ・ブロード・インスティテュート・インコーポレイテッ | 遺伝子産物の発現を変更するためのCRISPR−Cas系および方法 |
JP2016501531A (ja) * | 2012-12-12 | 2016-01-21 | ザ・ブロード・インスティテュート・インコーポレイテッド | 配列操作および治療適用のための系、方法および組成物の送達、エンジニアリングおよび最適化 |
JP2016504026A (ja) * | 2012-12-12 | 2016-02-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 配列操作のための系、方法および最適化ガイド組成物のエンジニアリング |
JP2016521995A (ja) * | 2013-06-17 | 2016-07-28 | ザ・ブロード・インスティテュート・インコーポレイテッド | ウイルス成分を使用して障害および疾患をターゲティングするためのCRISPR−Cas系および組成物の送達、使用および治療上の適用 |
JP2017513510A (ja) * | 2014-04-28 | 2017-06-01 | リコンビネティクス・インコーポレイテッドRecombinetics,Inc. | ブタにおける多重遺伝子編集 |
JP2017534295A (ja) * | 2014-09-29 | 2017-11-24 | ザ ジャクソン ラボラトリー | エレクトロポレーションによる遺伝子改変哺乳動物の高効率ハイスループット生成 |
JP2019511236A (ja) * | 2016-04-15 | 2019-04-25 | メモリアル スローン ケタリング キャンサー センター | トランスジェニックt細胞及びキメラ抗原受容体t細胞組成物及び関連方法 |
US10494621B2 (en) | 2015-06-18 | 2019-12-03 | The Broad Institute, Inc. | Crispr enzyme mutations reducing off-target effects |
US10550372B2 (en) | 2013-12-12 | 2020-02-04 | The Broad Institute, Inc. | Systems, methods and compositions for sequence manipulation with optimized functional CRISPR-Cas systems |
US10577630B2 (en) | 2013-06-17 | 2020-03-03 | The Broad Institute, Inc. | Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy |
US10696986B2 (en) | 2014-12-12 | 2020-06-30 | The Board Institute, Inc. | Protected guide RNAS (PGRNAS) |
US10711285B2 (en) | 2013-06-17 | 2020-07-14 | The Broad Institute, Inc. | Optimized CRISPR-Cas double nickase systems, methods and compositions for sequence manipulation |
US10781444B2 (en) | 2013-06-17 | 2020-09-22 | The Broad Institute, Inc. | Functional genomics using CRISPR-Cas systems, compositions, methods, screens and applications thereof |
US10851357B2 (en) | 2013-12-12 | 2020-12-01 | The Broad Institute, Inc. | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
US10930367B2 (en) | 2012-12-12 | 2021-02-23 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for Cas enzymes or CRISPR-Cas systems for target sequences and conveying results thereof |
US11008588B2 (en) | 2013-06-17 | 2021-05-18 | The Broad Institute, Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
JP2021166513A (ja) * | 2012-12-12 | 2021-10-21 | ザ・ブロード・インスティテュート・インコーポレイテッド | 配列操作のためのCRISPR−Cas成分系、方法および組成物 |
US11155795B2 (en) | 2013-12-12 | 2021-10-26 | The Broad Institute, Inc. | CRISPR-Cas systems, crystal structure and uses thereof |
US11407985B2 (en) | 2013-12-12 | 2022-08-09 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for genome editing |
US11578312B2 (en) | 2015-06-18 | 2023-02-14 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of CAS9 orthologs and variants for sequence manipulation |
Families Citing this family (167)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120196370A1 (en) * | 2010-12-03 | 2012-08-02 | Fyodor Urnov | Methods and compositions for targeted genomic deletion |
CA2745031C (en) * | 2008-12-04 | 2018-08-14 | Sangamo Biosciences, Inc. | Genome editing in rats using zinc-finger nucleases |
US20110023152A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genome editing of cognition related genes in animals |
US20110023148A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genome editing of addiction-related genes in animals |
US20110023154A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Silkworm genome editing with zinc finger nucleases |
US20110023139A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in cardiovascular disease |
US20110023141A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved with parkinson's disease |
US20110023153A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in alzheimer's disease |
US20110023150A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genome editing of genes associated with schizophrenia in animals |
US20110023151A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genome editing of abc transporters |
US20110023144A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in amyotrophyic lateral sclerosis disease |
US20110023156A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Feline genome editing with zinc finger nucleases |
US20110016539A1 (en) * | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genome editing of neurotransmission-related genes in animals |
US20110023140A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Rabbit genome editing with zinc finger nucleases |
US20110016540A1 (en) * | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genome editing of genes associated with trinucleotide repeat expansion disorders in animals |
US20110030072A1 (en) * | 2008-12-04 | 2011-02-03 | Sigma-Aldrich Co. | Genome editing of immunodeficiency genes in animals |
US20110016541A1 (en) * | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genome editing of sensory-related genes in animals |
US20110023143A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of neurodevelopmental genes in animals |
US20110016543A1 (en) * | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genomic editing of genes involved in inflammation |
US20110023158A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Bovine genome editing with zinc finger nucleases |
US20110023145A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in autism spectrum disorders |
US20110023146A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in secretase-associated disorders |
US20110023149A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of genes involved in tumor suppression in animals |
US20110023147A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genomic editing of prion disorder-related genes in animals |
US20110016546A1 (en) * | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Porcine genome editing with zinc finger nucleases |
EP2206723A1 (en) | 2009-01-12 | 2010-07-14 | Bonas, Ulla | Modular DNA-binding domains |
US20110239315A1 (en) | 2009-01-12 | 2011-09-29 | Ulla Bonas | Modular dna-binding domains and methods of use |
US9314005B2 (en) | 2009-07-01 | 2016-04-19 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for severe combined immunodeficiency (SCID) |
WO2011051390A1 (en) | 2009-10-28 | 2011-05-05 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Homologous recombination in the oocyte |
EP2580331A4 (en) * | 2010-06-14 | 2013-11-27 | Univ Iowa State Res Found Inc | NUCLEASE ACTIVITY OF THE TAL EFFECTOR AND FUSION PROTEIN FOKI |
US9175280B2 (en) | 2010-10-12 | 2015-11-03 | Sangamo Biosciences, Inc. | Methods and compositions for treating hemophilia B |
WO2012082509A2 (en) * | 2010-12-15 | 2012-06-21 | Sigma-Aldrich Co. Llc | Biomarkers for enhanced protein production |
US20130316391A1 (en) | 2010-12-29 | 2013-11-28 | Sigmaaldrich Co., LLC | Cells having disrupted expression of proteins involved in adme and toxicology processes |
CN102559652A (zh) * | 2010-12-31 | 2012-07-11 | 中国人民解放军第三军医大学 | 整合缺陷型慢病毒在制备锌指核酸酶于动物早期胚胎表达的介导剂中的应用及方法 |
SG194089A1 (en) | 2011-04-27 | 2013-11-29 | Amyris Inc | Methods for genomic modification |
US9150847B2 (en) | 2011-09-21 | 2015-10-06 | Sangamo Biosciences, Inc. | Methods and compositions for regulation of transgene expression |
CA3099582A1 (en) | 2011-10-27 | 2013-05-02 | Sangamo Biosciences, Inc. | Methods and compositions for modification of the hprt locus |
WO2013086008A1 (en) * | 2011-12-05 | 2013-06-13 | Factor Bioscience Inc. | Methods and products for transfecting cells |
US20130216579A1 (en) * | 2012-01-23 | 2013-08-22 | The Trustees Of Columbia University In The City Of New York | Methods and compostitions for gene editing of a pathogen |
PL2847335T3 (pl) | 2012-04-25 | 2019-01-31 | Regeneron Pharmaceuticals, Inc. | Celowanie dużymi wektorami do celowania wspomagane nukleazą |
CN104471067B (zh) | 2012-05-07 | 2020-08-14 | 桑格摩生物治疗股份有限公司 | 用于核酸酶介导的转基因靶向整合的方法和组合物 |
JP6329537B2 (ja) | 2012-07-11 | 2018-05-23 | サンガモ セラピューティクス, インコーポレイテッド | 生物学的薬剤の送達のための方法および組成物 |
HUE051612T2 (hu) | 2012-07-11 | 2021-03-01 | Sangamo Therapeutics Inc | Eljárások és készítmények lizoszomális tárolási betegségek kezelésére |
US10648001B2 (en) | 2012-07-11 | 2020-05-12 | Sangamo Therapeutics, Inc. | Method of treating mucopolysaccharidosis type I or II |
SG10201701601WA (en) | 2012-08-29 | 2017-04-27 | Sangamo Biosciences Inc | Methods and compositions for treatment of a genetic condition |
EP2906684B8 (en) | 2012-10-10 | 2020-09-02 | Sangamo Therapeutics, Inc. | T cell modifying compounds and uses thereof |
WO2014089212A1 (en) | 2012-12-05 | 2014-06-12 | Sangamo Biosciences, Inc. | Methods and compositions for regulation of metabolic disorders |
BR112015019950B1 (pt) | 2013-02-20 | 2023-02-14 | Regeneron Pharmaceuticals, Inc | Método para gerar linhagem de células-tronco embrionárias (es) de rato, e, cultura in vitro |
CA2901676C (en) | 2013-02-25 | 2023-08-22 | Sangamo Biosciences, Inc. | Methods and compositions for enhancing nuclease-mediated gene disruption |
WO2014153470A2 (en) | 2013-03-21 | 2014-09-25 | Sangamo Biosciences, Inc. | Targeted disruption of t cell receptor genes using engineered zinc finger protein nucleases |
US20160186208A1 (en) * | 2013-04-16 | 2016-06-30 | Whitehead Institute For Biomedical Research | Methods of Mutating, Modifying or Modulating Nucleic Acid in a Cell or Nonhuman Mammal |
RU2676708C2 (ru) | 2013-04-16 | 2019-01-10 | Регенерон Фармасьютикалс, Инк. | Направленная модификация генома крысы |
AU2014262867B2 (en) | 2013-05-10 | 2019-12-05 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
CN105683376A (zh) | 2013-05-15 | 2016-06-15 | 桑格摩生物科学股份有限公司 | 用于治疗遗传病状的方法和组合物 |
EP3039136B8 (en) | 2013-08-28 | 2020-12-16 | Sangamo Therapeutics, Inc. | Compositions for linking dna-binding domains and cleavage domains |
EP3057432B1 (en) | 2013-10-17 | 2018-11-21 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering in hematopoietic stem cells |
CA3194037A1 (en) | 2013-10-17 | 2015-04-23 | Sangamo Biosciences, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
JP2016537341A (ja) | 2013-11-11 | 2016-12-01 | サンガモ バイオサイエンシーズ, インコーポレイテッド | ハンチントン病を処置するための方法および組成物 |
PL3068881T3 (pl) | 2013-11-13 | 2019-08-30 | Children's Medical Center Corporation | Regulacja ekspresji genów, w której pośredniczą nukleazy |
CA3229275A1 (en) | 2013-12-09 | 2015-06-18 | Sangamo Biosciences, Inc. | Methods and compositions for genome engineering |
JP6174811B2 (ja) | 2013-12-11 | 2017-08-02 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ゲノムの標的改変のための方法及び組成物 |
EP3083958B1 (en) | 2013-12-19 | 2019-04-17 | Amyris, Inc. | Methods for genomic integration |
DK3102673T3 (da) | 2014-02-03 | 2020-07-06 | Sangamo Therapeutics Inc | Fremgangsmåder og sammensætninger til behandling af beta-talassæmi |
AU2015218576B2 (en) | 2014-02-24 | 2020-02-27 | Sangamo Therapeutics, Inc. | Methods and compositions for nuclease-mediated targeted integration |
EP3929279A1 (en) | 2014-03-18 | 2021-12-29 | Sangamo Therapeutics, Inc. | Methods and compositions for regulation of zinc finger protein expression |
WO2015164748A1 (en) | 2014-04-24 | 2015-10-29 | Sangamo Biosciences, Inc. | Engineered transcription activator like effector (tale) proteins |
JP6571679B2 (ja) | 2014-04-25 | 2019-09-04 | トランスレイト バイオ, インコーポレイテッド | メッセンジャーrnaの精製方法 |
AU2015255877B2 (en) | 2014-05-08 | 2020-03-26 | Chdi Foundation, Inc. | Methods and compositions for treating huntington's disease |
AU2015259191B2 (en) | 2014-05-13 | 2019-03-21 | Sangamo Therapeutics, Inc. | Methods and compositions for prevention or treatment of a disease |
WO2015188065A1 (en) | 2014-06-05 | 2015-12-10 | Sangamo Biosciences, Inc. | Methods and compositions for nuclease design |
MX2016016133A (es) | 2014-06-06 | 2017-08-04 | Regeneron Pharma | Métodos y composiciones para modificar un locus dirigido. |
EP3461885B1 (en) | 2014-06-26 | 2021-10-20 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for targeted genetic modifications and methods of use |
WO2016014794A1 (en) | 2014-07-25 | 2016-01-28 | Sangamo Biosciences, Inc. | Methods and compositions for modulating nuclease-mediated genome engineering in hematopoietic stem cells |
WO2016014837A1 (en) | 2014-07-25 | 2016-01-28 | Sangamo Biosciences, Inc. | Gene editing for hiv gene therapy |
US9616090B2 (en) | 2014-07-30 | 2017-04-11 | Sangamo Biosciences, Inc. | Gene correction of SCID-related genes in hematopoietic stem and progenitor cells |
WO2016025759A1 (en) | 2014-08-14 | 2016-02-18 | Shen Yuelei | Dna knock-in system |
PT3194570T (pt) | 2014-09-16 | 2021-08-06 | Sangamo Therapeutics Inc | Métodos e composições para manipulação e correção de genoma mediada por nuclease em células estaminais hematopoiéticas |
BR112017008022A2 (pt) | 2014-10-23 | 2018-02-20 | Regeneron Pharmaceuticals, Inc. | célula, polinucleotídeo, veículo, e, métodos para modificação de um genoma de células cho e para preparação de uma proteína de interesse. |
JP6727199B2 (ja) | 2014-11-21 | 2020-07-22 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ガイドrnaのペアを使用したターゲティングによる遺伝子改変の方法及び組成物 |
CN104450785A (zh) * | 2014-12-08 | 2015-03-25 | 复旦大学 | 使用编码靶向核酸内切酶附着体载体的基因组编辑方法及试剂盒 |
US10889834B2 (en) | 2014-12-15 | 2021-01-12 | Sangamo Therapeutics, Inc. | Methods and compositions for enhancing targeted transgene integration |
ES2760508T3 (es) | 2014-12-19 | 2020-05-14 | Regeneron Pharma | Métodos y composiciones para la modificación genética dirigida a través de la transformación múltiple en una sola etapa |
CN107406842B (zh) * | 2015-01-09 | 2021-05-11 | 生物辐射实验室股份有限公司 | 检测基因组编辑 |
EP3247366A4 (en) | 2015-01-21 | 2018-10-31 | Sangamo Therapeutics, Inc. | Methods and compositions for identification of highly specific nucleases |
WO2016128549A1 (en) | 2015-02-13 | 2016-08-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Polypeptides for engineering integrase chimeric proteins and their use in gene therapy |
US10179918B2 (en) | 2015-05-07 | 2019-01-15 | Sangamo Therapeutics, Inc. | Methods and compositions for increasing transgene activity |
SG10202112057QA (en) | 2015-05-12 | 2021-12-30 | Sangamo Therapeutics Inc | Nuclease-mediated regulation of gene expression |
US9957501B2 (en) | 2015-06-18 | 2018-05-01 | Sangamo Therapeutics, Inc. | Nuclease-mediated regulation of gene expression |
CA2991301A1 (en) | 2015-07-13 | 2017-01-19 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
CA2998500A1 (en) | 2015-09-23 | 2017-03-30 | Sangamo Therapeutics, Inc. | Htt repressors and uses thereof |
AU2016343887B2 (en) | 2015-10-28 | 2023-04-06 | Sangamo Therapeutics, Inc. | Liver-specific constructs, factor VIII expression cassettes and methods of use thereof |
CA3004349A1 (en) | 2015-11-23 | 2017-06-01 | Sangamo Therapeutics, Inc. | Methods and compositions for engineering immunity |
AU2016374253B2 (en) | 2015-12-18 | 2021-10-21 | Sangamo Therapeutics, Inc. | Targeted disruption of the MHC cell receptor |
US11352631B2 (en) | 2015-12-18 | 2022-06-07 | Sangamo Therapeutics, Inc. | Targeted disruption of the T cell receptor |
JP6930052B2 (ja) | 2016-01-15 | 2021-09-01 | サンガモ セラピューティクス, インコーポレイテッド | 神経性疾患の処置のための方法および組成物 |
AU2016391970B2 (en) | 2016-02-02 | 2024-02-22 | Sangamo Therapeutics, Inc. | Compositions for linking DNA-binding domains and cleavage domains |
WO2017143071A1 (en) | 2016-02-18 | 2017-08-24 | The Regents Of The University Of California | Methods and compositions for gene editing in stem cells |
JP2019515654A (ja) | 2016-03-16 | 2019-06-13 | ザ ジェイ. デヴィッド グラッドストーン インスティテューツ | 肥満及び/又は糖尿病を処置するための方法及び組成物、並びに候補処置薬剤を識別するための方法及び組成物 |
WO2017165655A1 (en) * | 2016-03-23 | 2017-09-28 | Dana-Farber Cancer Institute, Inc. | Methods for enhancing the efficiency of gene editing |
WO2017201311A2 (en) | 2016-05-18 | 2017-11-23 | Amyris, Inc. | Compositions and methods for genomic integration of nucleic acids into exogenous landing pads |
JP7203014B2 (ja) | 2016-08-24 | 2023-01-12 | サンガモ セラピューティクス, インコーポレイテッド | 工学操作されたヌクレアーゼを使用した遺伝子発現の調節 |
EP3504327B1 (en) | 2016-08-24 | 2021-10-06 | Sangamo Therapeutics, Inc. | Engineered target specific nucleases |
EP3509645A4 (en) * | 2016-09-07 | 2020-06-17 | Sangamo Therapeutics, Inc. | MODULATION OF LIVER GENES |
JP7042263B2 (ja) | 2016-10-20 | 2022-03-25 | サンガモ セラピューティクス, インコーポレイテッド | ファブリー病の治療のための方法および組成物 |
EP3532106A4 (en) | 2016-10-31 | 2020-06-24 | Sangamo Therapeutics, Inc. | GENE CORRECTION OF SCID-RELATED GENES IN HEMATOPOIETIC AND PROGENITANT STEM CELLS |
WO2018112278A1 (en) | 2016-12-14 | 2018-06-21 | Ligandal, Inc. | Methods and compositions for nucleic acid and protein payload delivery |
CA3061612A1 (en) | 2017-04-28 | 2018-11-01 | Acuitas Therapeutics, Inc. | Novel carbonyl lipids and lipid nanoparticle formulations for delivery of nucleic acids |
RU2019139045A (ru) | 2017-05-03 | 2021-06-03 | Сангамо Терапьютикс, Инк. | Способы и композиции для модификации гена регулятора трансмембранной проводимости при кистозном фиброзе (cftr) |
US11512287B2 (en) | 2017-06-16 | 2022-11-29 | Sangamo Therapeutics, Inc. | Targeted disruption of T cell and/or HLA receptors |
SG11202004003YA (en) | 2017-11-09 | 2020-05-28 | Sangamo Therapeutics Inc | Genetic modification of cytokine inducible sh2-containing protein (cish) gene |
KR20200118468A (ko) | 2018-02-08 | 2020-10-15 | 상가모 테라퓨틱스, 인코포레이티드 | 조작된 표적 특이적 뉴클레아제 |
CN112041432A (zh) | 2018-02-15 | 2020-12-04 | 纪念斯隆-凯特林癌症中心 | Foxp3靶向剂组合物以及用于过继细胞疗法的使用方法 |
AU2019239880B2 (en) | 2018-03-19 | 2023-11-30 | Regeneron Pharmaceuticals, Inc. | Transcription modulation in animals using CRISPR/Cas systems |
US20210015869A1 (en) | 2018-04-05 | 2021-01-21 | Juno Therapeutics, Inc. | T cells expressing a recombinant receptor, related polynucleotides and methods |
CA3094468A1 (en) | 2018-04-05 | 2019-10-10 | Juno Therapeutics, Inc. | Methods of producing cells expressing a recombinant receptor and related compositions |
EP3781677A4 (en) | 2018-04-16 | 2022-01-19 | University of Massachusetts | COMPOSITIONS AND METHODS FOR IMPROVED GENE EDITTING |
US11421007B2 (en) | 2018-04-18 | 2022-08-23 | Sangamo Therapeutics, Inc. | Zinc finger protein compositions for modulation of huntingtin (Htt) |
US11690921B2 (en) | 2018-05-18 | 2023-07-04 | Sangamo Therapeutics, Inc. | Delivery of target specific nucleases |
CN112867792A (zh) | 2018-08-23 | 2021-05-28 | 桑格摩生物治疗股份有限公司 | 工程化靶特异性碱基编辑器 |
EP3849565A4 (en) | 2018-09-12 | 2022-12-28 | Fred Hutchinson Cancer Research Center | REDUCING CD33 EXPRESSION FOR SELECTIVE PROTECTION OF THERAPEUTIC CELLS |
KR20210060533A (ko) | 2018-09-18 | 2021-05-26 | 상가모 테라퓨틱스, 인코포레이티드 | 프로그램화된 세포 사멸 1 (pd1) 특이적 뉴클레아제 |
WO2020069029A1 (en) | 2018-09-26 | 2020-04-02 | Emendobio Inc. | Novel crispr nucleases |
EP3867376A1 (en) | 2018-10-18 | 2021-08-25 | Intellia Therapeutics, Inc. | Nucleic acid constructs and methods of use |
CN113166727A (zh) | 2018-11-28 | 2021-07-23 | 四十七公司 | 对消融方案耐受的基因修饰的hspc |
KR20210138569A (ko) | 2019-01-11 | 2021-11-19 | 아퀴타스 테라퓨틱스 인크. | 활성제의 지질 나노입자 전달을 위한 지질 |
WO2020163379A1 (en) | 2019-02-05 | 2020-08-13 | Emendobio Inc. | Crispr compositions and methods for promoting gene editing of ribosomal protein s19 (rps19) gene |
US20220154157A1 (en) | 2019-02-06 | 2022-05-19 | Emendobio Inc. | New engineered high fidelity cas9 |
US20220145330A1 (en) | 2019-02-10 | 2022-05-12 | The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Glads | Modified mitochondrion and methods of use thereof |
CA3133361A1 (en) | 2019-04-03 | 2020-10-08 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for insertion of antibody coding sequences into a safe harbor locus |
WO2020223535A1 (en) | 2019-05-01 | 2020-11-05 | Juno Therapeutics, Inc. | Cells expressing a recombinant receptor from a modified tgfbr2 locus, related polynucleotides and methods |
JP2022531577A (ja) | 2019-05-01 | 2022-07-07 | ジュノー セラピューティクス インコーポレイテッド | 改変されたcd247遺伝子座からキメラ受容体を発現する細胞、関連ポリヌクレオチド、および方法 |
US20220348912A1 (en) | 2019-06-20 | 2022-11-03 | University Of Massachusetts | Compositions and methods for improved gene editing |
EP3994270A1 (en) | 2019-07-02 | 2022-05-11 | Fred Hutchinson Cancer Research Center | Recombinant ad35 vectors and related gene therapy improvements |
WO2021072115A1 (en) | 2019-10-08 | 2021-04-15 | Regents Of The University Of Minnesota | Crispr-mediated human genome editing with vectors |
CA3156277A1 (en) | 2019-11-08 | 2021-05-14 | Regeneron Pharmaceuticals, Inc. | CRISPR-VAA STRATEGIES FOR THE THERAPY OF X-LINKED JUVENILE RETINOSCHISIS |
WO2021195079A1 (en) | 2020-03-23 | 2021-09-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use |
CA3172449A1 (en) | 2020-03-27 | 2021-09-30 | Erik Hans MANTING | Ex vivo use of modified cells of leukemic origin for enhancing the efficacy of adoptive cell therapy |
US20230181641A1 (en) | 2020-05-13 | 2023-06-15 | Juno Therapeutics, Inc. | Process for producing donor-batched cells expressing a recombinant receptor |
GB202007577D0 (en) | 2020-05-21 | 2020-07-08 | Oxford Genetics Ltd | Hdr enhancers |
EP4153741A1 (en) | 2020-05-21 | 2023-03-29 | Oxford Genetics Limited | Hdr enhancers |
US20230183750A1 (en) | 2020-05-21 | 2023-06-15 | Oxford Genetics Limited | Hdr enhancers |
GB202007578D0 (en) | 2020-05-21 | 2020-07-08 | Univ Oxford Innovation Ltd | Hdr enhancers |
JP2023531531A (ja) | 2020-06-26 | 2023-07-24 | ジュノ セラピューティクス ゲーエムベーハー | 組換え受容体を条件付きで発現する操作されたt細胞、関連ポリヌクレオチド、および方法 |
US20230374483A1 (en) | 2020-07-08 | 2023-11-23 | Regents Of The University Of Minnesota | Modified hexosaminidase and uses thereof |
AU2021308681A1 (en) | 2020-07-16 | 2023-03-09 | Acuitas Therapeutics, Inc. | Cationic lipids for use in lipid nanoparticles |
JP2023549780A (ja) | 2020-11-04 | 2023-11-29 | ジュノー セラピューティクス インコーポレイテッド | 改変されたインバリアントcd3免疫グロブリンスーパーファミリー鎖遺伝子座からキメラ受容体を発現する細胞ならびに関連するポリヌクレオチドおよび方法 |
KR20230157388A (ko) | 2021-03-12 | 2023-11-16 | 멘두스 비.브이. | 백신접종의 방법 및 cd47 차단의 용도 |
JP2024511414A (ja) | 2021-03-23 | 2024-03-13 | アイオバンス バイオセラピューティクス,インコーポレイテッド | 腫瘍浸潤リンパ球のcish遺伝子編集及び免疫療法におけるその使用 |
EP4426832A1 (en) | 2021-11-03 | 2024-09-11 | The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone | Precise genome editing using retrons |
WO2023081900A1 (en) | 2021-11-08 | 2023-05-11 | Juno Therapeutics, Inc. | Engineered t cells expressing a recombinant t cell receptor (tcr) and related systems and methods |
WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
IL314482A (en) | 2022-02-02 | 2024-09-01 | Regeneron Pharma | Anti-TFR:GAA and anti-CD63:GAA insertions for the treatment of Pompe disease |
WO2023150798A1 (en) | 2022-02-07 | 2023-08-10 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for defining optimal treatment timeframes in lysosomal disease |
WO2023150393A2 (en) | 2022-02-07 | 2023-08-10 | Ensoma, Inc. | Inhibitor-resistant mgmt modifications and modification of mgmt-encoding nucleic acids |
AU2023218391A1 (en) | 2022-02-11 | 2024-07-11 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for screening 4r tau targeting agents |
WO2023220040A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus with a modified capsid for gene therapy |
WO2023220035A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus compositions and methods for gene therapy |
WO2023220043A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus with a modified genome for gene therapy |
CN114891772B (zh) * | 2022-05-27 | 2023-07-14 | 湖南福来格生物技术有限公司 | 一种去乙酰基酶突变体及其应用 |
WO2024026474A1 (en) | 2022-07-29 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle |
WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
WO2024073606A1 (en) | 2022-09-28 | 2024-04-04 | Regeneron Pharmaceuticals, Inc. | Antibody resistant modified receptors to enhance cell-based therapies |
WO2024094084A1 (en) * | 2022-11-01 | 2024-05-10 | Huidagene Therapeutics Co., Ltd. | Iscb polypeptides and uses thereof |
US20240182561A1 (en) | 2022-11-04 | 2024-06-06 | Regeneron Pharmaceuticals, Inc. | Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle |
WO2024100604A1 (en) | 2022-11-09 | 2024-05-16 | Juno Therapeutics Gmbh | Methods for manufacturing engineered immune cells |
US20240173426A1 (en) | 2022-11-14 | 2024-05-30 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes |
WO2024160989A1 (en) | 2023-02-03 | 2024-08-08 | Syngenta Crop Protection Ag | Herbicide resistant plants |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005519631A (ja) * | 2002-01-23 | 2005-07-07 | ザ ユニバーシティ オブ ユタ リサーチ ファウンデーション | ジンクフィンガーヌクレアーゼを用いる、標的化された染色体変異誘発 |
Family Cites Families (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4186183A (en) | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
US4261975A (en) | 1979-09-19 | 1981-04-14 | Merck & Co., Inc. | Viral liposome particle |
US4485054A (en) | 1982-10-04 | 1984-11-27 | Lipoderm Pharmaceuticals Limited | Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV) |
US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US5049386A (en) | 1985-01-07 | 1991-09-17 | Syntex (U.S.A.) Inc. | N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4774085A (en) | 1985-07-09 | 1988-09-27 | 501 Board of Regents, Univ. of Texas | Pharmaceutical administration systems containing a mixture of immunomodulators |
US5422251A (en) | 1986-11-26 | 1995-06-06 | Princeton University | Triple-stranded nucleic acids |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5176996A (en) | 1988-12-20 | 1993-01-05 | Baylor College Of Medicine | Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
WO1991017424A1 (en) | 1990-05-03 | 1991-11-14 | Vical, Inc. | Intracellular delivery of biologically active substances by means of self-assembling lipid complexes |
US5420032A (en) | 1991-12-23 | 1995-05-30 | Universitge Laval | Homing endonuclease which originates from chlamydomonas eugametos and recognizes and cleaves a 15, 17 or 19 degenerate double stranded nucleotide sequence |
US5436150A (en) | 1992-04-03 | 1995-07-25 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoities (foki) restriction endonuclease |
US5356802A (en) | 1992-04-03 | 1994-10-18 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoites (FokI) restriction endonuclease |
US5487994A (en) | 1992-04-03 | 1996-01-30 | The Johns Hopkins University | Insertion and deletion mutants of FokI restriction endonuclease |
US5792632A (en) | 1992-05-05 | 1998-08-11 | Institut Pasteur | Nucleotide sequence encoding the enzyme I-SceI and the uses thereof |
US6242568B1 (en) | 1994-01-18 | 2001-06-05 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
US6140466A (en) | 1994-01-18 | 2000-10-31 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
CA2181548C (en) | 1994-01-18 | 2009-11-03 | Carlos F. Barbas, Iii | Zinc finger protein derivatives and methods therefor |
CA2186118C (en) | 1994-03-23 | 2010-10-19 | Richard W. Hanson | Compacted nucleic acids and their delivery to cells |
US5585245A (en) | 1994-04-22 | 1996-12-17 | California Institute Of Technology | Ubiquitin-based split protein sensor |
USRE45721E1 (en) | 1994-08-20 | 2015-10-06 | Gendaq, Ltd. | Relating to binding proteins for recognition of DNA |
GB9824544D0 (en) | 1998-11-09 | 1999-01-06 | Medical Res Council | Screening system |
US5789538A (en) | 1995-02-03 | 1998-08-04 | Massachusetts Institute Of Technology | Zinc finger proteins with high affinity new DNA binding specificities |
US5925523A (en) | 1996-08-23 | 1999-07-20 | President & Fellows Of Harvard College | Intraction trap assay, reagents and uses thereof |
GB2338237B (en) | 1997-02-18 | 2001-02-28 | Actinova Ltd | In vitro peptide or protein expression library |
GB9703369D0 (en) | 1997-02-18 | 1997-04-09 | Lindqvist Bjorn H | Process |
US6342345B1 (en) | 1997-04-02 | 2002-01-29 | The Board Of Trustees Of The Leland Stanford Junior University | Detection of molecular interactions by reporter subunit complementation |
GB9710807D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
US6410248B1 (en) | 1998-01-30 | 2002-06-25 | Massachusetts Institute Of Technology | General strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites |
EP1060261B1 (en) | 1998-03-02 | 2010-05-05 | Massachusetts Institute of Technology | Poly zinc finger proteins with improved linkers |
US6140081A (en) | 1998-10-16 | 2000-10-31 | The Scripps Research Institute | Zinc finger binding domains for GNN |
US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
US7013219B2 (en) | 1999-01-12 | 2006-03-14 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
AU2982900A (en) * | 1999-02-03 | 2000-08-25 | Children's Medical Center Corporation | Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site |
US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
US7257541B1 (en) | 1999-10-08 | 2007-08-14 | I2 Technologies Us, Inc. | System and method for performing a business process in a multi-enterprise, collaborating network |
AU776576B2 (en) | 1999-12-06 | 2004-09-16 | Sangamo Biosciences, Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
ATE483970T1 (de) | 2000-02-08 | 2010-10-15 | Sangamo Biosciences Inc | Zellen zur entdeckung von medikamenten |
US20020061512A1 (en) | 2000-02-18 | 2002-05-23 | Kim Jin-Soo | Zinc finger domains and methods of identifying same |
US20030044787A1 (en) | 2000-05-16 | 2003-03-06 | Joung J. Keith | Methods and compositions for interaction trap assays |
JP2002060786A (ja) | 2000-08-23 | 2002-02-26 | Kao Corp | 硬質表面用殺菌防汚剤 |
GB0108491D0 (en) | 2001-04-04 | 2001-05-23 | Gendaq Ltd | Engineering zinc fingers |
US20040224385A1 (en) | 2001-08-20 | 2004-11-11 | Barbas Carlos F | Zinc finger binding domains for cnn |
ATE531796T1 (de) * | 2002-03-21 | 2011-11-15 | Sangamo Biosciences Inc | Verfahren und zusammensetzungen zur verwendung von zinkfinger-endonukleasen zur verbesserung der homologen rekombination |
EP1348335A1 (en) | 2002-03-28 | 2003-10-01 | Boehringer Ingelheim International GmbH | Non-human transgenic mammals and their use as a disease model |
US6793480B2 (en) * | 2002-07-01 | 2004-09-21 | John Dominka | Shutoff valve assembly |
US9447434B2 (en) | 2002-09-05 | 2016-09-20 | California Institute Of Technology | Use of chimeric nucleases to stimulate gene targeting |
US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
US8409861B2 (en) | 2003-08-08 | 2013-04-02 | Sangamo Biosciences, Inc. | Targeted deletion of cellular DNA sequences |
US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
CA2579677A1 (en) | 2004-09-16 | 2006-03-30 | Sangamo Biosciences, Inc. | Compositions and methods for protein production |
AU2006272634B2 (en) | 2005-07-26 | 2013-01-24 | Sangamo Therapeutics, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
US20080015164A1 (en) | 2006-05-19 | 2008-01-17 | Sangamo Biosciences, Inc. | Methods and compositions for inactivation of dihydrofolate reductase |
JP5551432B2 (ja) | 2006-05-25 | 2014-07-16 | サンガモ バイオサイエンシーズ, インコーポレイテッド | 遺伝子不活性化のための方法と組成物 |
JP5266210B2 (ja) | 2006-05-25 | 2013-08-21 | サンガモ バイオサイエンシズ インコーポレイテッド | 改変開裂ハーフドメイン |
CA2684378C (en) | 2007-04-26 | 2016-11-29 | Sangamo Biosciences, Inc. | Targeted integration into the ppp1r12c locus |
LT2602323T (lt) * | 2007-06-01 | 2018-04-10 | Open Monoclonal Technology, Inc. | Kompozicijos ir būdai endogeninių imunoglobulinų genams slopinti ir transgeniniams žmogaus idiotipo antikūnams gaminti |
KR101657504B1 (ko) | 2007-09-27 | 2016-09-19 | 상가모 바이오사이언스 인코포레이티드 | 생물학적으로 활성인 뉴클레아제의 신속한 생체내 확인 |
JP5702144B2 (ja) * | 2007-09-27 | 2015-04-15 | ダウ アグロサイエンシィズ エルエルシー | 5−エノールピルビルシキミ酸−3−リン酸シンターゼ遺伝子をターゲッティングする改変ジンクフィンガータンパク質 |
CA2745031C (en) * | 2008-12-04 | 2018-08-14 | Sangamo Biosciences, Inc. | Genome editing in rats using zinc-finger nucleases |
-
2009
- 2009-12-03 CA CA2745031A patent/CA2745031C/en active Active
- 2009-12-03 ES ES09830727.5T patent/ES2627552T3/es active Active
- 2009-12-03 US US12/592,852 patent/US9206404B2/en active Active
- 2009-12-03 WO PCT/US2009/006365 patent/WO2010065123A1/en active Application Filing
- 2009-12-03 KR KR1020117015171A patent/KR101803737B1/ko active IP Right Grant
- 2009-12-03 SG SG2011040789A patent/SG172760A1/en unknown
- 2009-12-03 EP EP16200237.2A patent/EP3156494B8/en active Active
- 2009-12-03 JP JP2011539509A patent/JP5681114B2/ja active Active
- 2009-12-03 AU AU2009322964A patent/AU2009322964B2/en active Active
- 2009-12-03 CN CN200980154833.0A patent/CN102625655B/zh active Active
- 2009-12-03 EP EP09830727.5A patent/EP2352369B1/en active Active
-
2015
- 2015-11-19 US US14/946,224 patent/US20190062789A9/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005519631A (ja) * | 2002-01-23 | 2005-07-07 | ザ ユニバーシティ オブ ユタ リサーチ ファウンデーション | ジンクフィンガーヌクレアーゼを用いる、標的化された染色体変異誘発 |
Non-Patent Citations (3)
Title |
---|
JPN6014015851; Nature Biotechnol. Vol.23, No.8, 2005, p.967-973 * |
JPN6014015852; Nature Biotechnol. Vol.25, No.7, 2007, p.778-785 * |
JPN6014015853; Nature Vol.435, No.7042, 2005, p.646-651 * |
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US11597919B2 (en) | 2013-12-12 | 2023-03-07 | The Broad Institute Inc. | Systems, methods and compositions for sequence manipulation with optimized functional CRISPR-Cas systems |
US11407985B2 (en) | 2013-12-12 | 2022-08-09 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for genome editing |
US10550372B2 (en) | 2013-12-12 | 2020-02-04 | The Broad Institute, Inc. | Systems, methods and compositions for sequence manipulation with optimized functional CRISPR-Cas systems |
US10851357B2 (en) | 2013-12-12 | 2020-12-01 | The Broad Institute, Inc. | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
US11591581B2 (en) | 2013-12-12 | 2023-02-28 | The Broad Institute, Inc. | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
CN111647627A (zh) * | 2014-04-28 | 2020-09-11 | 重组股份有限公司 | 多重基因编辑 |
US12070022B2 (en) | 2014-04-28 | 2024-08-27 | Recombinetics, Inc. | Methods for making genetic edits |
JP2017513510A (ja) * | 2014-04-28 | 2017-06-01 | リコンビネティクス・インコーポレイテッドRecombinetics,Inc. | ブタにおける多重遺伝子編集 |
JP2017534295A (ja) * | 2014-09-29 | 2017-11-24 | ザ ジャクソン ラボラトリー | エレクトロポレーションによる遺伝子改変哺乳動物の高効率ハイスループット生成 |
US10696986B2 (en) | 2014-12-12 | 2020-06-30 | The Board Institute, Inc. | Protected guide RNAS (PGRNAS) |
US11624078B2 (en) | 2014-12-12 | 2023-04-11 | The Broad Institute, Inc. | Protected guide RNAS (pgRNAS) |
US10494621B2 (en) | 2015-06-18 | 2019-12-03 | The Broad Institute, Inc. | Crispr enzyme mutations reducing off-target effects |
US11578312B2 (en) | 2015-06-18 | 2023-02-14 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of CAS9 orthologs and variants for sequence manipulation |
US10876100B2 (en) | 2015-06-18 | 2020-12-29 | The Broad Institute, Inc. | Crispr enzyme mutations reducing off-target effects |
US11377637B2 (en) | 2016-04-15 | 2022-07-05 | Memorial Sloan Kettering Cancer Center | Transgenic T cell and chimeric antigen receptor T cell compositions and related methods |
JP7058223B2 (ja) | 2016-04-15 | 2022-04-21 | メモリアル スローン ケタリング キャンサー センター | トランスジェニックt細胞及びキメラ抗原受容体t細胞組成物及び関連方法 |
JP2019511236A (ja) * | 2016-04-15 | 2019-04-25 | メモリアル スローン ケタリング キャンサー センター | トランスジェニックt細胞及びキメラ抗原受容体t細胞組成物及び関連方法 |
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SG172760A1 (en) | 2011-08-29 |
CN102625655B (zh) | 2016-07-06 |
ES2627552T3 (es) | 2017-07-28 |
EP3156494A1 (en) | 2017-04-19 |
CA2745031A1 (en) | 2010-06-10 |
EP2352369A4 (en) | 2012-05-02 |
EP2352369A1 (en) | 2011-08-10 |
EP3156494B1 (en) | 2018-04-25 |
US20160068865A1 (en) | 2016-03-10 |
US20100218264A1 (en) | 2010-08-26 |
EP3156494B8 (en) | 2018-09-19 |
US9206404B2 (en) | 2015-12-08 |
CN102625655A (zh) | 2012-08-01 |
KR20110101175A (ko) | 2011-09-15 |
AU2009322964A1 (en) | 2010-06-10 |
KR101803737B1 (ko) | 2017-12-01 |
US20190062789A9 (en) | 2019-02-28 |
WO2010065123A1 (en) | 2010-06-10 |
AU2009322964B2 (en) | 2014-10-09 |
JP5681114B2 (ja) | 2015-03-04 |
CA2745031C (en) | 2018-08-14 |
EP2352369B1 (en) | 2017-04-26 |
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