CELL-SPECIFIC MOLECULE AND METHOD FOR IMPORTING DNA INTO OSTEOBLAST NUCLEI

摘要

A plasmid, viral or linear DNA molecule containing a nucleic acid sequence derived from the promoter region of the hColla2 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 (Cbfal/Runx2) gene. The Cbfal/Runx2 promoter can be added to the sequence derived from, or alternatively, comprising the promoter region of the hColla2 gene. Also provided are methods of use of the novel sequences.