公开(公告)号：US07741113B2

公开(公告)日：2010-06-22

申请号：US11410579

申请日：2006-04-24

申请人： Donna D. Strong ,  Thomas A. Linkhart ,  David A. Dean

发明人： Donna D. Strong ,  Thomas A. Linkhart ,  David A. Dean

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12N5/00 ,  C12N15/63

CPC分类号： A61K48/0058 ,  C07K14/4702 ,  C07K2319/09 ,  C12N15/85 ,  C12N2800/30 ,  C12N2830/001 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/42 ,  C12N2830/85 ,  C12N2840/20

摘要： A plasmid, viral or linear DNA molecule containing a nucleic acid sequence derived from the promoter region of the hCol1α2 gene, which is selectively transported into the nuclei of cells in the osteoblast lineage. The sequence can be used independently as a nuclear entry sequence only, and/or as a nuclear entry sequence without regard to position, in a vector or linear DNA that directs gene expression and nuclear entry. The disclosure further includes a chimeric DNA sequence derived by the addition of osteoblast-specific enhancer sequences to the nuclear entry sequence/promoter sequence, to increase osteoblast-specific expression while retaining osteoblast-specific nuclear import. An enhancer sequence is derived from the promoter region of the human Core Binding Factor alpha 1 (Cbfa1/Runx2) gene. The Cbfa1/Runx2 promoter can be added to the sequence derived from, or alternatively, comprising the promoter region of the hCol1α2 gene. Also provided are methods of use of the novel sequences.

摘要翻译： 含有衍生自hCol1α2基因的启动子区域的核酸序列的质粒，病毒或线性DNA分子，其被选择性地转运到成骨细胞谱系中的细胞核中。 该序列可以独立地用作核进入序列，和/或作为指导基因表达和核进入的载体或线性DNA中不考虑位置的核进入序列。 本公开还包括通过向核进入序列/启动子序列添加成骨细胞特异性增强子序列而衍生的嵌合DNA序列，以增加成骨细胞特异性表达，同时保留成骨细胞特异性核进口。 增强子序列衍生自人核心结合因子α1（Cbfa1 / Runx2）基因的启动子区。 可以将Cbfa1 / Runx2启动子加入到由hCol1α2基因的启动子区域衍生或替代地包含hCol1α2基因的启动子区域的序列中。 还提供了使用新序列的方法。