申请人:——
公开号:US20030195162A1
公开(公告)日:2003-10-16
Disclosed are isolated polynucleotides containing nucleic acid segments encoding human or murine ATP sulfurylase/APS kinase, also known as PAPS synthetase (PAPSS), particularly PAPSS2 and Papss2 proteins. Also disclosed are nucleic acid constructs, including vectors, probes, primers, and primer pairs containing novel PAPSS2 and Papss2 gene sequences. A genetically modified vertebrate cell containing a nucleic acid construct of the present invention and a non-human vertebrate comprising the cell are also disclosed. Based on the present PAPSS2-specific polynucleotides and nucleic acid constructs, are genetic testing kits and methods for diagnosing spondyloepimetaphyseal dysplasia (SEMD) in a human subject, of identifying a human carrier of an heritable allele associated with SEMD, and of gene therapy or protein therapy for treating a human subject having an osteoarthritic disorder, which is caused or aggravated by deficient enzymatic sulfation activity. Also disclosed is a protein therapy method for treating a human subject having an osteoarthritic disorder caused or aggravated by deficient enzymatic sulfation activity that employs an inventive PAPSS2 fusion protein. Also disclosed are an isolated antibody or antibody fragment that selectively binds a PAPSS2 or Papss2 protein.
所公开的是分离的多核苷酸,其含有编码人或鼠 ATP 硫磷酸酶/APS 激酶(又称 PAPS 合成酶 (PAPSS)),特别是 PAPSS2 和 Papss2 蛋白的核酸片段。还公开了核酸构建体,包括载体、探针、引物和含有新型 PAPSS2 和 Papss2 基因序列的引物对。还公开了含有本发明核酸构建体的转基因脊椎动物细胞和包含该细胞的非人脊椎动物。基于本发明的 PAPSS2 特异性多核苷酸和核酸构建体,公开了用于诊断人类脊柱软骨骺端发育不良(SEMD)的基因检测试剂盒和方法、用于鉴定与 SEMD 相关的遗传等位基因的人类携带者的基因检测试剂盒和方法、以及用于治疗人类骨关节炎疾病的基因治疗或蛋白质治疗的基因检测试剂盒和方法,该骨关节炎疾病是由酶硫酸化活性不足引起或加重的。还公开了一种蛋白质治疗方法,用于治疗因酶硫化活性不足而引起或加重的人类骨关节炎疾病,该方法采用了本发明的 PAPSS2 融合蛋白。还公开了一种选择性结合 PAPSS2 或 Papss2 蛋白的分离抗体或抗体片段。