US2003143731A1PendingUtilityA1

Use of heterologous transcription factors in gene therapy

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Assignee: ARIAD GENE THERAPEUTICS INCPriority: Jun 27, 1995Filed: Oct 23, 2001Published: Jul 31, 2003
Est. expiryJun 27, 2015(expired)· nominal 20-yr term from priority
Inventors:Michael Z. GilmanSridaran Natesan
C07K 2319/00C07K 14/005C07K 14/4702C12N 2710/16622
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Claims

Abstract

This invention provides novel materials and methods involving the heterologous expression of transcription factors which are useful for effecting transcription of target genes in genetically engineered cells or organisms containing them. Target gene constructs and other materials useful for practicing the invention are also disclosed.

Claims

exact text as granted — not AI-modified
1 . A method for expressing a target gene in a cell within a host organism which comprises introducing into the organism cells containing: 
 (a) a transcription factor construct containing a first heterologous DNA sequence encoding and capable of expressing a transcription factor capable of activating transcription of a gene linked to a transcription control sequence responsive to the transcription factor, and    (b) a target gene construct containing a second heterologous DNA sequence comprising a target gene operably linked to a transcription control sequence comprising a DNA promoter sequence and one or more copies of a DNA recognition sequence permitting gene transcription responsive to the presence of the transcription factor.    
     
     
         2 . A method of  claim 1  in which the cell is of human origin.  
     
     
         3 . A method of  claim 1  in which the host organism is a human.  
     
     
         4 . A method of  claim 1  in which the transcription factor comprises one or more domains having a peptide sequence derived from a naturally occurring human peptide sequence.  
     
     
         5 . A method of  claim 1  in which the transcription factor comprises peptide sequence derived from a DNA-binding protein of human origin.  
     
     
         6 . A method of  claim 1  in which the transcription factor comprises a composite DNA-binding domain.  
     
     
         7 . A method of  claim 1  in which the transcription factor comprises peptide sequence derived from a transcription activating protein of human origin.  
     
     
         8 . A method of  claim 7  in which the transcription factor contains one or more copies of peptide sequence comprising all or part of the peptide sequence spanning positions 361 through 550 of human NF-kB p65, or a peptide sequence derived therefrom.  
     
     
         9 . A method of  claim 7  or  8  in which the transcription factor contains one or more copies of peptide sequence comprising all or part of the peptide sequence spanning positions 361 through 450 of human NF-kB p65, or a peptide sequence derived therefrom.  
     
     
         10 . A method of  claim 9  in which the transcription factor contains one or more copies of the peptide sequence p65(361-550), or peptide sequence derived therefrom.  
     
     
         11 . A method of  claim 8  in which the transcription factor comprises a composite transcription activation domain.  
     
     
         12 . A method of  claim 11  in which the composite transcription activation domain comprises: 
 (a) one or more copies of a peptide sequence comprising all or a portion of the peptide sequence spanning positions 361-450 of human NF-kB p65, or peptide sequence derived therefrom, and  
 (b) one or more copies of a heterologous peptide sequence which potentiates the transcription activation potency of the transcription factor  
 
     
     
         13 . A method of  claim 12  in which the heterologous peptide sequence is selected or derived from peptide sequence within the sequence of VP16 V8, VP16 C, HSF, or CTF.  
     
     
         14 . A method of  claim 1  in which the DNA sequence encoding the transcription factor and the DNA sequence encoding the target gene are both operably linked to transcription control sequences permitting gene expression responsive to the presence of the transcription factor.  
     
     
         15 . A method of  claim 1  in which the DNAs are introduced into the cell by calcium phosphate precipitation, DEAE dextran-DNA complexation, fusion, electroporation, biolistics, transfection, or lipofection.  
     
     
         16 . A method of  claim 15  in which the DNAs are present in one or more viral vectors.  
     
     
         17 . A method of  claim 1  in which the cells are encapsulated within a semipermeable membrane.  
     
     
         18 . A method for expressing a target gene in a cell within a host organism which comprises introducing into the organism, under conditions permitting DNA uptake by one or more cells within the organism: 
 (a) a transcription factor construct containing a first heterologous DNA sequence encoding and capable of expressing a transcription factor capable of activating transcription of a gene linked to a transcription control sequence responsive to the transcription factor, and    (b) a target gene construct containing a second heterologous DNA sequence comprising a target gene operably linked to a transcription control sequence comprising a DNA promoter sequence and one or more copies of a DNA recognition sequence permitting gene transcription responsive to the presence of the transcription factor.    
     
     
         19 . A method of  claim 18  in which the host organism is mammalian.  
     
     
         20 . A method of  claim 19  in which the host organism is a human subject.  
     
     
         21 . A method of  claim 20  in which the transcription factor comprises one or more domains having a peptide sequence derived from a naturally occurring human peptide sequence.  
     
     
         22 . A method of  claim 20  in which the transcription factor comprises peptide sequence derived from a DNA-binding protein of human origin.  
     
     
         23 . A method of  claim 20  in which the transcription factor comprises a composite DNA-binding domain.  
     
     
         24 . A method of  claim 20  in which the transcription factor comprises peptide sequence derived from a transcription activating protein of human origin.  
     
     
         25 . A method of  claim 24  in which the transcription factor contains one or more copies of peptide sequence comprising all or part of the peptide sequence spanning positions 361 through 550 of human NF-kB p65, or a peptide sequence derived therefrom.  
     
     
         26 . A method of  claim 25  in which the transcription factor contains one or more copies of peptide sequence comprising all or part of the peptide sequence spanning positions 361 through 450 of human NF-kB p65, or a peptide sequence derived therefrom.  
     
     
         27 . A method of  claim 26  in which the transcription factor contains one or more copies of the peptide sequence p65(361-550), or peptide sequence derived therefrom.  
     
     
         28 . A method of  claim 25  in which the transcription factor comprises a composite transcription activation domain.  
     
     
         29 . A method of  claim 28  in which the composite transcription activation domain comprises: 
 (a) one or more copies of a peptide sequence comprising all or a portion of the peptide sequence spanning positions 361-450 of human NF-kB p65, or peptide sequence derived therefrom, and  
 (b) one or more copies of a heterologous peptide sequence which potentiates the transcription activation potency of the transcription factor  
 
     
     
         30 . A method of  claim 29  in which the heterologous peptide sequence is selected or derived from peptide sequence within the sequence of VP16 V8, VP16 C, HSF, or CTF.  
     
     
         31 . A method of  claim 20  in which the DNA sequence encoding the transcription factor and the DNA sequence encoding the target gene are both operably linked to transcription control sequences permitting gene expression responsive to the presence of the transcription factor.  
     
     
         32 . A method of  claim 20  in which the two DNA constructs are present in one or more viral vectors.  
     
     
         33 . A recombinant DNA sequence encoding a chimeric transcription factor containing one or more copies of peptide sequence comprising all or part of the peptide sequence spanning positions 361 through 550 of human NF-kB p65, or a peptide sequence derived therefrom, and peptide sequence heterologous thereto.  
     
     
         34 . A recombinant DNA sequence of  claim 33  in which the p65 peptide sequence comprises peptide sequence selected or derived from the p65 sequence spanning positions 361 through 450.  
     
     
         35 . A recombinant DNA sequence of  claim 33  in which the transcription factor contains one or more copies of a heterologous peptide sequence which potentiates the transcription activation potency of the transcription factor.  
     
     
         36 . A recombinant DNA sequence of  claim 35  in which the heterologous peptide sequence is selected or derived from peptide sequence within the sequence of VP16 V8, VP16 C, HSF, or CTF.  
     
     
         37 . A cell containing a recombinant DNA sequence of any of claims  33  through 36.

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