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公开(公告)号：EP4347035A1
公开(公告)日：2024-04-10
申请号：EP22816704.5
申请日：2022-05-31
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公开(公告)号：EP3237611A2
公开(公告)日：2017-11-01
申请号：EP15874317.9
申请日：2015-12-22
发明人： WOLFE, Scot, Andrew , BOLUKBASI, Mehmet, Fatih , GUPTA, Ankit , SONTHEIMER, Erik, J. , AMRANI, Nadia
CPC分类号： C12N9/22 , C07K2319/80 , C12Y301/00
摘要： The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage. A robust, broadly applicable strategy is disclosed to impart Cas9 genome-editing systems with the single-genomic-site accuracy needed for safe, effective clinical application.
摘要翻译： 本发明提供了促进人类基因组内单个位点核酸酶基因编辑精确度的Cas9平台。 例如，Cas9核酸酶/ DN-A-靶向单元（Cas9-DTU）融合蛋白将Cas9 / sgRNA复合物精确地递送至基因组内的特定靶位点，用于随后的相邻靶序列的sgRNA依赖性切割。 或者，使用对原型间隔相邻基序（PAM）识别结构域的突变来减弱Cas9结合使得Cas9靶标位点识别依赖于相关联的DTU，同时保留了Cas9的sgRNA介导的DNA切割保真度。 与标准Cas9系统相比，Cas9-DTU融合蛋白具有改善的靶位点结合精确度，更高的核酸酶活性和更广泛的序列靶向范围。 现有的Cas9或sgRNA变体（例如，截短的sgRNA（tru-gRNA），切口酶和FokI融合体）与这些改进相容以进一步减少脱靶切割。 公开了一种强大的，广泛适用的策略，为Cas9基因组编辑系统提供安全，有效的临床应用所需的单基因组位点准确性。
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公开(公告)号：EP4349978A3
公开(公告)日：2024-07-24
申请号：EP23212741.5
申请日：2015-12-22
发明人： WOLFE, Scot, Andrew , BOLUKBASI, Mehmet, Fatih , GUPTA, Ankit , SONTHEIMER, Erik, J. , AMRANI, Nadia
CPC分类号： C07K2319/8020130101 , C12N9/22 , C12Y301/00
摘要： The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage. A robust, broadly applicable strategy is disclosed to impart Cas9 genome-editing systems with the single-genomic-site accuracy needed for safe, effective clinical application.
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公开(公告)号：EP4349978A2
公开(公告)日：2024-04-10
申请号：EP23212741.5
申请日：2015-12-22
发明人： WOLFE, Scot, Andrew , BOLUKBASI, Mehmet, Fatih , GUPTA, Ankit , SONTHEIMER, Erik, J. , AMRANI, Nadia
IPC分类号： C12N9/14
摘要： The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage. A robust, broadly applicable strategy is disclosed to impart Cas9 genome-editing systems with the single-genomic-site accuracy needed for safe, effective clinical application.
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