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1. 发明申请

US20060242725A1 Cell-specific molecule and method for importing DNA into osteoblast nuclei 有权
标题翻译：细胞特异性分子和将DNA导入成骨细胞核的方法
公开(公告)号：US20060242725A1
公开(公告)日：2006-10-26
申请号：US11410579
申请日：2006-04-24
申请人： Donna Strong , Thomas Linkhart , David Dean
发明人： Donna Strong , Thomas Linkhart , David Dean
IPC分类号： A61K48/00 , A01K67/027 , C12Q1/68 , C07H21/04
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：含有源自hCol1alpha2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入。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hCol1alpha2基因的启动子区域衍生或替代地包含hCol1alpha2基因的启动子区域的序列中。还提供了使用新序列的方法。

2. 发明申请

US20070212332A1 Methods for accelerating bone repair 审中-公开
标题翻译：加速骨修复的方法
公开(公告)号：US20070212332A1
公开(公告)日：2007-09-13
申请号：US11503365
申请日：2006-08-10
申请人： David Baylink , Charles Rundle , Kin-Hing Lau , Donna Strong , Shin-Tai Chen , Thomas Linkhart
发明人： David Baylink , Charles Rundle , Kin-Hing Lau , Donna Strong , Shin-Tai Chen , Thomas Linkhart
IPC分类号： A61K48/00
CPC分类号： C12N9/0083 , A61K48/005 , C07K14/51 , C12N2799/027 , C12Y114/99001
摘要： Vectors, such as retroviral vectors and transposon-based nonviral vectors, are disclosed herein that can be used to target transgene expression to the proliferating periosteal cells and cells in the marrow space after bone fracture. In one embodiment, these vectors include a human Cox-2 gene that is modified to improve mRNA stability and protein translation by truncating the 3′ untranslated region (UTR). In addition, in some embodiments, the native translation signal is replaced with an optimized Kozak sequence. These vectors can be used alone or with vectors expressing BMP2/4, FGF-2, or LMP-1 gene to repair bone fractures and increase prostaglandin secretion. Methods for identifying agents that accelerate bone repair are also disclosed.
摘要翻译：本文公开了载体，例如逆转录病毒载体和基于转座子的非病毒载体，其可以用于靶向骨骨折后骨髓空间中增殖性骨膜细胞和细胞的转基因表达。在一个实施方案中，这些载体包括通过截短3'非翻译区（UTR）修饰以改善mRNA稳定性和蛋白质翻译的人Cox-2基因。此外，在一些实施例中，用优化的Kozak序列替换天文翻译信号。这些载体可以单独使用或与使用表达BMP2 / 4，FGF-2或LMP-1基因的载体一起使用来修复骨折并增加前列腺素分泌。还公开了用于鉴定促进骨修复的药剂的方法。

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