HS-40 enhancer-containing vector

Abstract

A viral expression vector having a nucleic acid which includes ( 1 ) a transcriptional start site; ( 2 ) a promoter operably linked to the transcriptional start site; and ( 3 ) an enhancer operably linked to the promoter, the enhancer comprising the DNA sequence of SEQ ID NO:1 or the RNA equivalent thereof.

What is claimed is:  
     
         1 . A viral expression vector comprising a nucleic acid which comprises (1) a transcriptional start site; (2) a promoter operably linked to the transcriptional start site; and (3) an enhancer operably linked to the promoter, the enhancer comprising the DNA sequence of SEQ ID NO:1 or the RNA equivalent thereof.  
     
     
         2 . The viral expression vector of  claim 1 , wherein the vector is a retrovirus.  
     
     
         3 . The viral expression vector of  claim 1 , wherein the promoter drives transcription of a mRNA encoding a polypeptide, the transcription beginning from the transcriptional start site.  
     
     
         4 . The viral expression vector of  claim 3 , wherein the polypeptide is a growth hormone.  
     
     
         5 . The viral expression vector of  claim 1 , wherein the promoter is a tissue-specific promoter.  
     
     
         6 . The viral expression vector of  claim 5 , wherein the promoter is a ζ-globin promoter.  
     
     
         7 . The viral expression vector of  claim 1 , wherein the enhancer comprises SEQ ID NO:2 or the RNA equivalent thereof.  
     
     
         8 . The viral expression vector of  claim 7 , wherein the enhancer comprises SEQ ID NO:3 or the RNA equivalent thereof.  
     
     
         9 . The viral expression vector of  claim 1 , wherein the nucleic acid further comprises a transcriptional termination signal that terminates transcription from the transcriptional start site.  
     
     
         10 . The viral expression vector of  claim 9 , wherein the vector is a retrovirus.  
     
     
         11 . The viral expression vector of  claim 9 , wherein the promoter drives transcription of a mRNA encoding a polypeptide, the transcription beginning from the transcriptional start site.  
     
     
         12 . The viral expression vector of  claim 9 , wherein the transcriptional termination signal is a polyadenylation signal.  
     
     
         13 . A transgenic animal whose somatic and germ line cells contain at least one copy of a transgene comprising (1) a transcriptional start site; (2) a promoter operably linked to the transcriptional start site; and (3) an enhancer operably linked to the promoter, the enhancer comprising the nucleotide sequence of SEQ ID NO:1, wherein the transgenic animal expresses a transcript driven by the promoter, the level of expression in at least one cell type of the animal being proportionally dependent on the copy number of the transgene.  
     
     
         14 . The transgenic animal of  claim 13 , wherein the animal is a rodent.  
     
     
         15 . The transgenic animal of  claim 14 , wherein the animal is a mouse.  
     
     
         16 . The transgenic animal of  claim 15 , wherein the somatic and germ line cells contain more than 5 copies of the transgene.  
     
     
         17 . The transgenic animal of  claim 16 , wherein the somatic and germ line cells contain more than 15 copies of the transgene.  
     
     
         18 . The transgenic animal of  claim 17 , wherein the promoter drives transcription of a mRNA encoding a polypeptide, the transcription beginning from the transcriptional start site.  
     
     
         19 . The transgenic animal of  claim 18 , wherein the polypeptide is a growth hormone.  
     
     
         20 . The transgenic animal of  claim 19 , wherein the promoter is a ζ-globin promoter, and the at least one cell type is a erythroblast.  
     
     
         21 . The transgenic animal of  claim 20 , wherein the enhancer comprises SEQ ID NO:2.  
     
     
         22 . The transgenic animal of  claim 21 , wherein the enhancer comprises SEQ ID NO:3.  
     
     
         23 . A method of expressing a transcript in an animal, the method comprising administering to the animal a nucleic acid comprising (1) a transcriptional start site for the transcript; (2) a promoter operably linked to the transcriptional start site; and (3) an enhancer operably linked to the promoter, the enhancer comprising the DNA sequence of SEQ ID NO:1 or the RNA equivalent thereof.  
     
     
         24 . The method of  claim 23 , wherein the nucleic acid is administered by parenteral injection.  
     
     
         25 . The method of  claim 23 , wherein the nucleic acid is administered via a viral expression vector.  
     
     
         26 . The method of  claim 23 , wherein the transcript is a mRNA encoding a polypeptide.  
     
     
         27 . The method of  claim 26 , wherein the polypeptide is a growth hormone.  
     
     
         28 . The method of  claim 23 , wherein the promoter is a ζ-globin promoter.  
     
     
         29 . The method of  claim 23 , wherein the enhancer comprises SEQ ID NO:2 or the RNA equivalent thereof.  
     
     
         30 . The method of  claim 23 , wherein the enhancer comprises SEQ ID NO:3 or the RNA equivalent thereof.  
     
     
         31 . The method of  claim 23 , wherein the nucleic acid further comprises a transcriptional termination signal.  
     
     
         32 . The method of claim  31 , wherein the transcriptional termination signal is a polyadenylation signal.