公开(公告)号：US09388412B2

公开(公告)日：2016-07-12

申请号：US14408189

申请日：2013-06-14

Applicant: THE GENERAL HOSPITAL CORPORATION

Inventor： Kenneth D. Bloch ,  Pankaj Arora ,  Christopher Newton-Cheh ,  Thomas J. Wang

IPC: A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/11 ,  C12Q1/68 ,  A61K31/7088 ,  A61K45/06

CPC classification number: C12N15/113 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/00 ,  C12N15/111 ,  C12N2310/113 ,  C12N2320/31 ,  C12N2320/34 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/178

Abstract: The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject. Other aspects of the present invention relates to assays, methods and systems to identify a subject at risk of hypertension, or identifying a subject suitable to administration of an anti-miR-425 agent for treatment of hypertension, the assay comprising assessing if a subject is homozygous or heterozygous for the major (A) allele of rs5068 SNP, and/or assaying for levels of miR-425 and/or assaying for levels of NT-proANP and/or levels of ANP in the plasma of a subject.

Abstract translation: 本发明涉及用于治疗受试者中的高血压和其它心血管疾病的方法，试剂盒和组合物，特别是治疗或预防受试者心血管疾病的方法，包括向受试者施用至少一种抗miR剂至miRNA -425。 在一些实施方案中，抗miR剂是与SEQ ID NO：1的至少一部分miR-425互补的小分子或寡核苷酸，或与至少部分miRNA种子序列AUGACA互补的抗miR SEQ ID NO：2）。 本发明的另一方面涉及治疗受试者的低血压的方法，试剂盒和组合物，其包括施用包含miR-425试剂的组合物以降低受试者的ANP水平。 本发明的其它方面涉及用于鉴定患有高血压危险的受试者或鉴定适合于施用抗miR-425药物以治疗高血压的受试者的测定，方法和系统，所述测定包括评估受试者是否为 对于rs5068 SNP的主要（A）等位基因，和/或测定miR-425的水平和/或测定受试者血浆中NT-proANP水平和/或ANP水平的纯合或杂合。

公开(公告)号：US20150133521A1

公开(公告)日：2015-05-14

申请号：US14408189

申请日：2013-06-14

Applicant: THE GENERAL HOSPITAL CORPORATION

Inventor： Kenneth D. Bloch ,  Pankaj Arora ,  Christopher Newton-Cheh ,  Thomas J. Wang

IPC: C12N15/113 ,  A61K45/06 ,  C12Q1/68 ,  A61K31/7088

CPC classification number: C12N15/113 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/00 ,  C12N15/111 ,  C12N2310/113 ,  C12N2320/31 ,  C12N2320/34 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/178

Abstract: The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject. Other aspects of the present invention relates to assays, methods and systems to identify a subject at risk of hypertension, or identifying a subject suitable to administration of an anti-miR-425 agent for treatment of hypertension, the assay comprising assessing if a subject is homozygous or heterozygous for the major (A) allele of rs5068 SNP, and/or assaying for levels of miR-425 and/or assaying for levels of NT-proANP and/or levels of ANP in the plasma of a subject.

Abstract translation: 本发明涉及用于治疗受试者中的高血压和其它心血管疾病的方法，试剂盒和组合物，特别是治疗或预防受试者心血管疾病的方法，包括向受试者施用至少一种抗miR剂至miRNA -425。 在一些实施方案中，抗miR剂是与SEQ ID NO：1的至少一部分miR-425互补的小分子或寡核苷酸，或与至少部分miRNA种子序列AUGACA互补的抗miR SEQ ID NO：2）。 本发明的另一方面涉及治疗受试者的低血压的方法，试剂盒和组合物，其包括施用包含miR-425试剂的组合物以降低受试者的ANP水平。 本发明的其它方面涉及用于鉴定患有高血压危险的受试者或鉴定适于施用抗miR-425药物以治疗高血压的受试者的测定，方法和系统，所述测定包括评估受试者是否为 对于rs5068 SNP的主要（A）等位基因，和/或测定miR-425的水平和/或测定受试者血浆中NT-proANP水平和/或ANP水平的纯合或杂合。