Nucleic acid sequences of genes encoding high mobility group proteins and uses thereof

Abstract

The invention relates to DNA-sequences, their use and the use of DNA-sequences of the MAG gene or genes encoding the high mobility group proteins, agents for the treatment of various diseases including tumors, influencing the development of the vascular system, as well as for contraception and tissue regeneration, and appropriate kits and processes. The sequences, agents, uses, kits and processes enable the specific influencing of molecular mechanisms that jointly form the basis for various diseases, the development of the vascular system, the contraception and the regeneration of tissue. Thus, the disadvantages associated with other agents or processes are decreased.

What is claimed is:  
     
         1 . An isolated polynucleotide having a sequence comprising: 
 a first sequence encoding each of exons 1, 2 and 3 of an HMGI or MAG gene; and    a second sequence from a source other than an HMGI or MAG gene, said second sequence being from a human and being located upstream of said exons, said sequence also being a sequence other than a sequence immediately upstream of exon 1 of said HMGI or MAG gene in a human genome.    
     
     
         2 . An isolated polynucleotide according to  claim 1 , wherein said polynucleotide encodes a gene product which is encoded by one of SEQ ID NOS:1-19.  
     
     
         3 . An isolated polynucleotide according to  claim 1 , wherein said polynucleotide has a sequence of one of SEQ ID NOS:1-19.  
     
     
         4 . An isolated polypeptide having a sequence comprising: 
 a first sequence which is encoded by exons 1, 2 and 3 of an HMGI or MAG gene; and    a second sequence upstream of said first sequence, said sequence being encoded by a polynucleotide from a source other than an HMGI or MAG gene, said polynucleotide being from a human, said polynucleotide having a sequence other than a sequence immediately upstream of exon 1 of said HMGI or MAG gene in a human genome.    
     
     
         5 . An isolated polypeptide acccording to  claim 4 , wherein said polypeptide has a sequence encoded by one of SEQ ID NOS: 1-19.  
     
     
         6 . A method for treatment of tumors in a mammal, comprising administering to said mammal an agent which blocks the activity or effect of a DNA selected from the group consisting of an HMGI gene, a MAG gene and a polynucleotide having a sequence comprising: 
 a first sequence encoding each of exons 1, 2 and 3 of an HMGI or MAG gene; and    a second sequence from a source other than an HMGI or MAG gene, said second sequence being from a human and being located upstream of said exons, said sequence also being a sequence other than a sequence immediately upstream of exon 1 of said HMGI or MAG gene in a human genome, or which blocks the effect or activity of a transcription or translation product of said DNA.    
     
     
         7 . A method according to  claim 6 , wherein said DNA has a sequence of one of SEQ ID NOS:1-19 or a sequence encoding the same amino acids encoded by SEQ ID NOS:1-19.  
     
     
         8 . A method according  claim 6 , wherein said agent inhibits the formation of transcripts of the HMGI or MAG genes.  
     
     
         9 . A method according to  claim 6 , wherein said agent decreases the half-life of the HMGI or MAG gene transcripts.  
     
     
         10 . A method according to  claim 6 , wherein said agent is selected from the group consisting of anti-sense nucleic acid molecules and ribozymes.  
     
     
         11 . A method according to  claim 6 , wherein said agent is a translation product of said DNA.  
     
     
         12 . A method according to  claim 6 , wherein the administering step comprises incorporating said agent into the tumor.  
     
     
         13 . A method according to  claim 12 , wherein the administering step comprises: 
 introducing a vector to said tumor, said vector comprising said DNA or an RNA transcript thereof; and    expressing said DNA or RNA transcript to create translation products thereof which competitively inhibit binding of cellular HMGI/MAG gene translation products to the cellular genome.    
     
     
         14 . A method according to  claim 6 , wherein the tumor is one which shows expression of a gene which is selected from the group consisting of HMGI genes, HMGI-C genes and HMGI-Y genes.  
     
     
         15 . A method according to  claim 6 , wherein said agent is a nucleic acid having a sequence comprising at least one AT hook or at least one AT hook-like structure.  
     
     
         16 . A method for diagnosis of tumors, comprising: 
 administering to suspected tumor tissue a first polyncleotide complementary to a second polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said first polynucleotide and said second polynucleotide when a tumor is present, but not when a tumor is absent.    
     
     
         17 . A method according to  claim 16 , wherein said first polyncleotide additionally comprises a marker or label.  
     
     
         18 . A method for diagnosis of tumors, comprising: 
 administering to suspected tumor tissue a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said translation product and said polynucleotide when a tumor is present, but not when a tumor is absent.    
     
     
         19 . A method according to  claim 18 , wherein the translation product comprises a marker or label.  
     
     
         20 . A method for diagnosis of tumors, comprising: 
 administering to suspected tumor tissue an antibody to a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said antibodies and said translation products when a tumor is present, but not when a tumor is absent.    
     
     
         21 . A method according to  claim 20 , wherein the antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies and fragments and derivatives thereof.  
     
     
         22 . A method according to  claim 20 , wherein the antibody comprises a marker or label.  
     
     
         23 . A method for diagnosis of endometriosis, comprising: 
 administering a first polyncleotide to suspected ectopic endometrial tissue complementary to a second polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said first polynucleotide and said second polynucleotide when endometriosis is present, but not when endometriosis is absent.    
     
     
         24 . A method according to  claim 23 , wherein said first polyncleotide additionally comprises a marker or label.  
     
     
         25 . A method for diagnosis of endometriosis, comprising: 
 administering to suspected ectopic endometrial tissue a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said translation product and said polynucleotide when endometriosis is present, but not when endometriosis is absent.    
     
     
         26 . A method according to  claim 25 , wherein the translation product comprises a marker or label.  
     
     
         27 . A method for diagnosis of endometriosis, comprising: 
 administering to suspected ectopic endometrial tissue an antibody to a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    detecting significant complex formation between said antibodies and said translation products when endometriosis is present, but not when endometriosis is absent.    
     
     
         28 . A method according to  claim 27 , wherein the antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies and fragments and derivatives thereof.  
     
     
         29 . A method according to  claim 28 , wherein the antibody comprises a marker or label.  
     
     
         30 . A method for contraception in a mammal, comprising: 
 administering to said mammal a first polyncleotide complementary to a second polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said first polynucleotide and said second polynucleotide, thereby inhibiting fertility.    
     
     
         31 . A method for contraception in a mammal, comprising: 
 administering to said mammal a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said translation product and said polynucleotide thereby inhibiting fertility.    
     
     
         32 . A method for contraception in a mammal, comprising: 
 administering to said mammal an antibody to a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said antibodies and said translation products, thereby inhibiting fertility.    
     
     
         33 . A method according to  claim 32 , wherein the antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies and fragments and derivatives thereof.  
     
     
         34 . A method for regenerating tissue, comprising activating expression in said tissue of a nucleic acid sequence selected from the group consisting of HMGI genes, MAG genes, nucleic acid sequences according to SEQ ID Nos. 1-19 and their derivatives in a cell.  
     
     
         35 . A method according to  claim 34 , wherein the activating step comprises administering a phorbol ester.  
     
     
         36 . A method according to  claim 34 , wherein the activating step comprises administering said nucleic acid sequence in a vector.  
     
     
         37 . A method according to  claim 36 , wherein said nucleic acid sequence is under control of a promotor.  
     
     
         38 . A method according to  claim 37 , wherein the promotor is inducible, and the administering step additionally comprises administering an agent which induces said promoter.  
     
     
         39 . A method according to  claim 34 , wherein tissue regeneration occurs in situ.  
     
     
         40 . A method according to  claim 34 , wherein tissue regeneration is achieved by first carrying out the activating step in a cell which is then further propagated.  
     
     
         41 . A method according  claim 34 , wherein the tissue to be regenerated is mesenchymal tissue.  
     
     
         42 . A method according to  claim 46 , wherein the mesenchymal tissue is selected from the group comprising cartilage tissue, muscle tissue, fatty or adipose tissue, connective tissue and supporting tissue.  
     
     
         43 . A method for regenerating tissue, comprising administering to said tissue a translation product of a nucleic acid sequence selected from the group consisting of HMGI genes, MAG genes, nucleic acid sequences according to SEQ ID Nos. 1-19 and their derivatives.  
     
     
         44 . A method according to  claim 43 , wherein said translation product is administered via an encapsulation technique to said tissue.  
     
     
         45 . A method according to  claim 43 , wherein tissue is regenerated by first carrying out the administering step to a cell which is then further propagated.  
     
     
         46 . A method according to  claim 43 , wherein tissue regeneration is performed in situ.  
     
     
         47 . A method according  claim 43 , wherein the tissue to be regenerated is mesenchymal tissue.  
     
     
         48 . A method according to  claim 47 , wherein the mesenchymal tissue is selected from the group comprising cartilage tissue, muscle tissue, fatty or adipose tissue, connective tissue and supporting tissue.  
     
     
         49 . A method for inducing angiogenesis, comprising activating expression in venous or capillary tissue of a nucleic acid sequence selected from the group consisting of HMGI genes, MAG genes, nucleic acid sequences according to SEQ ID Nos. 1-19 and their derivatives in a cell.  
     
     
         50 . A method according to  claim 49 , wherein the activating step comprises administering a phorbol ester.  
     
     
         51 . A method according to  claim 49 , wherein the activating step comprises administering said nucleic acid sequence in a vector.  
     
     
         52 . A method according to  claim 51 , wherein said nucleic acid sequence is under control of a promotor.  
     
     
         53 . A method according to  claim 52 , wherein the promotor is inducible, and the administering step additionally comprises administering an agent which induces said promoter.  
     
     
         54 . A method according to  claim 49 , wherein angiogenesis occurs in situ.  
     
     
         55 . A method according to  claim 49 , wherein angiogenesis is achieved by first carrying out the activating step in a cell which is then further propagated.  
     
     
         56 . A method for improving vascular supply of myocardial tissue damaged by myocardial infarction, comprising inducing angiogenesis according to  claim 49 .  
     
     
         57 . A method for inducing angiogensis, comprising administering to venous or capillary tissue a translation product of a nucleic acid sequence selected from the group consisting of HMGI genes, MAG genes, nucleic acid sequences according to SEQ ID Nos. 1-19 and their derivatives.  
     
     
         58 . A method according to  claim 57 , wherein said translation product is administered via an encapsulation technique to said tissue.  
     
     
         59 . A method according to  claim 57 , wherein angiogenesis occurs by first carrying out the administering step to a cell which is then further propagated.  
     
     
         60 . A method according to  claim 57 , wherein angiogenesis occurs in situ.  
     
     
         61 . A method for improving vascular supply of myocardial tissue damaged by myocardial infarction, comprising inducing angiogenesis according to  claim 57 .  
     
     
         62 . A method for inhibiting angiogenesis in a mammal, comprising: 
 administering to said mammal a first polyncleotide complementary to a second polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said first polynucleotide and said second polynucleotide, thereby inhibiting angiogenesis.    
     
     
         63 . A method of preventing or treating loss of sight as a consequence of neovascularization, comprising inhibiting angiogenesis according to  claim 62 .  
     
     
         64 . A method for inhibiting angiogenesis in a mammal, comprising: 
 administering to said mammal a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said translation product and said polynucleotide thereby inhibiting angiogenesis.    
     
     
         65 . A method of preventing or treating loss of sight as a consequence of neovascularization, comprising inhibiting angiogenesis according to  claim 64 .  
     
     
         66 . A method for inhibiting angiogenesis in a mammal, comprising: 
 administering to said mammal an antibody to a translation product of a polyncleotide selected from the group consisting of HMGI genes, MAG genes and nucleic acid molecules having sequences according to one of SEQ ID NOS.: 1-19; and    forming a complex between said antibodies and said translation products, thereby inhibiting angiogenesis.    
     
     
         67 . A method according to  claim 64 , wherein the antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies and fragments and derivatives thereof.  
     
     
         68 . A method of preventing or treating loss of sight as a consequence of neovascularization, comprising inhibiting angiogenesis according to claim  66 .