公开(公告)号：US20110262399A1

公开(公告)日：2011-10-27

申请号：US13121532

申请日：2009-09-29

申请人： Antonio Fontanellas Romá ,  Gloria González Aseguinolaza ,  Maria Sol Rodriguez Pena ,  Maria Astrid Pañeda Rodriguez ,  Jaap Twisk ,  Jesús Maria Prieto Valtueña ,  Harald Petry ,  Sander Jan Hendrik Van Deventer

发明人： Antonio Fontanellas Romá ,  Gloria González Aseguinolaza ,  Maria Sol Rodriguez Pena ,  Maria Astrid Pañeda Rodriguez ,  Jaap Twisk ,  Jesús Maria Prieto Valtueña ,  Harald Petry ,  Sander Jan Hendrik Van Deventer

IPC分类号： A61K35/76 ,  A61P43/00 ,  C12N7/01 ,  C07H21/04 ,  C12N15/63

CPC分类号： C12N9/88 ,  A61K38/00 ,  A61K48/0058 ,  C12N2799/025 ,  C12Y205/01061

摘要： The present invention relates to nucleotide sequences coding for human porphobilinogen deaminase that are optimised for higher expression in mammalian cells. The invention further relates to DNA constructs comprising such optimised synthetic coding sequences for use in gene therapy of conditions caused by a deficiency in porphobilinogen deaminase, such as acute intermittent porphyria. Accordingly, the present invention relates to a nucleic acid or a nucleic acid construct comprising a nucleotide sequence coding for a human porphobilinogen deaminase, wherein at least 320 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 1 or wherein at least 305 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 3.

摘要翻译： 本发明涉及编码针对哺乳动物细胞中较高表达的人胆色素原脱氨酶的核苷酸序列。 本发明还涉及包含用于基因治疗由胆毒素原脱氨酶（例如急性间歇性卟啉症）缺乏引起的病症的优化的合成编码序列的DNA构建体。 因此，本发明涉及包含编码人胆色素原脱氨酶的核苷酸序列的核酸或核酸构建体，其中至少320个编码人胆色素原脱氨酶的密码子与SEQ ID NO：1中的密码子相同 或其中至少305个编码人胆色素原脱氨酶的密码子与SEQ ID NO：3中的密码子相同。

公开(公告)号：US08697665B2

公开(公告)日：2014-04-15

申请号：US13121532

申请日：2009-09-29

申请人： Antonio Fontanellas Romá ,  Gloria González Aseguinolaza ,  Maria Sol Rodriguez Pena ,  Maria Astrid Pañeda Rodriguez ,  Jaap Twisk ,  Jesús Maria Prieto Valtueña ,  Harald Petry ,  Sander Jan Hendrik Van Deventer

发明人： Antonio Fontanellas Romá ,  Gloria González Aseguinolaza ,  Maria Sol Rodriguez Pena ,  Maria Astrid Pañeda Rodriguez ,  Jaap Twisk ,  Jesús Maria Prieto Valtueña ,  Harald Petry ,  Sander Jan Hendrik Van Deventer

IPC分类号： A61K48/00 ,  C12N15/00

CPC分类号： C12N9/88 ,  A61K38/00 ,  A61K48/0058 ,  C12N2799/025 ,  C12Y205/01061

摘要： The present invention relates to nucleotide sequences coding for human porphobilinogen deaminase that are optimised for higher expression in mammalian cells. The invention further relates to DNA constructs comprising such optimised synthetic coding sequences for use in gene therapy of conditions caused by a deficiency in porphobilinogen deaminase, such as acute intermittent porphyria. Accordingly, the present invention relates to a nucleic acid or a nucleic acid construct comprising a nucleotide sequence coding for a human porphobilinogen deaminase, wherein at least 320 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 1 or wherein at least 305 of the codons coding for the human porphobilinogen deaminase are identical to the codons in SEQ ID NO: 3.

摘要翻译： 本发明涉及编码针对哺乳动物细胞中更高表达的人胆色素原脱氨酶的核苷酸序列。 本发明还涉及包含用于基因治疗由胆毒素原脱氨酶（例如急性间歇性卟啉症）缺乏引起的病症的优化的合成编码序列的DNA构建体。 因此，本发明涉及包含编码人胆色素原脱氨酶的核苷酸序列的核酸或核酸构建体，其中至少320个编码人胆色素原脱氨酶的密码子与SEQ ID NO：1中的密码子相同 或其中至少305个编码人胆色素原脱氨酶的密码子与SEQ ID NO：3中的密码子相同。

公开(公告)号：US20120225933A1

公开(公告)日：2012-09-06

申请号：US13508494

申请日：2010-11-04

申请人： Gloria González Aseguinolaza ,  Jesús María Prieto Valtueña ,  Lucía María Vanrell Majó

发明人： Gloria González Aseguinolaza ,  Jesús María Prieto Valtueña ,  Lucía María Vanrell Majó

IPC分类号： A61K31/713 ,  C12N15/86 ,  A61P35/00 ,  C12N15/113 ,  A61P1/16 ,  C12N15/85 ,  C12N5/10

CPC分类号： C12N15/635 ,  C12N2799/025 ,  C12N2830/003 ,  C12N2830/008

摘要： The application relates to gene constructs for inducible hepato-specific expression of polynucleotides of interest in response to an inducer agent, said constructs comprising (i) an inducible bi-directional operator-promoter with at least one responsive element to said inducer agent flanked by two hepato-specific promoters acting in divergent manner, (ii) a first nucleotide sequence encoding a transactivator which may be activated by said inducer agent operatively coupled to the first hepato-specific promoter and (iii) a second nucleotide sequence operatively coupled to the second hepato-specific promoter, wherein the promoters are induced as a consequence of the binding of the transactivator to the operator region of the operator-promoter in the presence of the inducer agent.

摘要翻译： 本申请涉及用于诱导型肝细胞特异性表达感兴趣的多核苷酸的基因构建体，所述基因构建体响应于诱导剂，所述构建体包含（i）具有至少一个对所述诱导剂的响应元件的诱导型双向操纵子启动子， （ii）编码反式激活因子的第一核苷酸序列，其可被所述诱导剂活化，所述诱导剂与第一肝特异性启动子有效偶联，和（iii）可操作地偶联至第二肝细胞的第二核苷酸序列 特异性启动子，其中由诱导剂存在下反式激活因子与操纵子启动子的操纵子区域的结合而诱导启动子。