Recombinant sequence, its preparation and use

Abstract

An isolated, purified or recombinant nucleic acid sequence is disclosed, comprising: (a) a sequence that encodes both an angiogenic factor antagonist and a vascular endothelial structure regulator; (b) a sequence substantially homologous to or that hybridises to sequence (a) under stringent conditions; or (c) a sequence substantially homologous to or that hybridises under stringent conditions to the sequence (a) or (b) but for the degeneracy of the genetic code; or (d) an oligonucleotide specific for any of the sequences (a), (b) or (c). Particular oligonucleotides (d) are those encoding the vascular endothelial structure regulator. Also described are methods for preparing the recombinant polynucleotide, proteins encoded by such polynucleotides and their use in gene or protein therapy for the treatment of conditions such as cancer.

1 . An isolated, purified or recombinant nucleic acid molecule (hereinafter ‘KV molecule’) comprising: a molecule that encodes both an angiogenic factor antagonist and a vascular endothelial structure regulator; or a homologue thereof.  
     
     
         2 . A nucleic acid molecule encoding two functionally distinct proteins wherein one of said proteins is an angiogenic factor antagonist and so acts to inhibit those factors that promote angiogenesis and the other of said proteins is a vascular endothelial structure regulator and so acts as a marker on endothelial ceslls to regulate endothelial structure.  
     
     
         3 . A molecule according to  claim 1 , wherein the angiogenic factor antagonist is derived from VEGF, bFGF, hepatocyte growth factor/scatter factor (HGF/SF) and/or chemokines.  
     
     
         4 . A molecule according to  claim 1 , wherein the endothelial structure regulator is derived from VE-cadherin, E-selectin, occludin, claudin-5 and/or vascular cell adhesion molecule (VCAM).  
     
     
         5 . A molecule according to  claim 1 , comprising KS 2101, KS2105, J6, J9 or J10, as defined herein.  
     
     
         6 . A molecule according to  claim 1 , comprising VC1, VC503, J11, J12 or J8, as defined herein.  
     
     
         7 . A molecule according to  claim 1 , comprising KVE702, J35, J36 or J37, as defined herein.  
     
     
         8 . A polypeptide sequence (hereinafter “KV protein”) encoded by a nucleic acid molecule according to  claim 1 .  
     
     
         9 . A polypeptide sequence according to  claim 8 , comprising KVE702 protein, J35 protein, J36 protein or J37 protein, as defined herein.  
     
     
         10 . A vector having incorporated expressibly therein a KV molecule according to  claim 1 .  
     
     
         11 . A cell, plasmid, virus, bacterium or other live organism having incorporated expressibly therein a KV molecule according to  claim 1   
     
     
         12 . A host cell transfected or transformed with a vector according to  claim 10 .  
     
     
         13 . The use of a host cell according to  claim 12  in the treatment or prevention of angoigenesis or cancer.  
     
     
         14 . The use of a KV protein according to  claim 8  in the preparation of a medicament for the treatment or prevention of angoigenesis or cancer.  
     
     
         15 . A formulation comprising a KV protein according to  claim 8  in association with a pharmaceuticlally acceptable carrier therefore.  
     
     
         16 . A method for the prophylaxis or treatment of a mammal, including man, comprising the administration to said mammal of a non-toxic, effective amount of a KV protein.