Therapeutic and diagnostic molecules

Abstract

The present invention relates to methods for modulating angiogenesis, comprising administering to a subject, or cells or tissue derived therefrom: (i) one or more miRNA, or precursors or variants thereof, wherein at least one of said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID N0:37) to inhibit angiogenesis; or (ii) one or more antagonists of a miRNA, wherein said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID N0:37) to promote or induce angiogenesis. Also provided are methods of diagnosis of conditions associated with abnormal angiogenesis, or determining predisposition thereto. Suitable pharmaceutical compositions are also provided.

1 . A method for decreasing endothelial cell permeability in a cell or tissue of a subject, the method comprising administering to the subject, or a cell or tissue derived therefrom, an effective amount of one or more antagonists of miR_27a. 
     
     
         2 . The method of  claim 1 , wherein the miR_27a is hsa_miR_27a and comprises the nucleotide sequence set forth in SEQ ID NO:1. 
     
     
         3 . The method of  claim 1 , wherein the antagonist is an antisense oligonucleotide specific for miR_27a. 
     
     
         4 . The method of  claim 3 , wherein the antisense oligonucleotide comprises a nucleotide sequence as set forth in SEQ ID NO:19. 
     
     
         5 . The method of  claim 3 , wherein the oligonucleotide comprises one or more modifications. 
     
     
         6 . The method of  claim 5 , wherein the oligonucleotide comprises any one or more of non-naturally occurring nucleotide analogues, non-phosphate linkages between nucleotides and conjugated moieties. 
     
     
         7 . A method for increasing the expression of VE-cadherin protein in a cell or tissue of a subject, the method comprising administering to the subject, or a cell or tissue derived therefrom, an effective amount of one or more antagonists of a miRNA comprising a seed region comprising the sequence UCACAGU (SEQ ID No. 37). 
     
     
         8 . The method of  claim 7 , wherein the miRNA comprising the seed region sequence UCACAGU is miR_27a. 
     
     
         9 . The method of  claim 8 , wherein the miR_27a is hsa_miR_27a and comprises the nucleotide sequence set forth in SEQ ID NO:1. 
     
     
         10 . The method of  claim 8 , wherein the antagonist is an antisense oligonucleotide specific for miR_27a. 
     
     
         11 . The method of  claim 10 , wherein the antisense oligonucleotide comprises a nucleotide sequence as set forth in SEQ ID NO:19. 
     
     
         12 . The method of  claim 10 , wherein the antisense oligonucleotide comprises one or more modifications. 
     
     
         13 . The method of  claim 12 , wherein the oligonucleotide comprises any one or more of non-naturally occurring nucleotide analogues, non-phosphate linkages between nucleotides and conjugated moieties. 
     
     
         14 . A method for increasing endothelial cell permeability in a cell or tissue of a subject, the method comprising administering to the subject, or a cell or tissue derived therefrom, an effective amount of a miRNA comprising a seed region comprising the sequence UCACAGU (SEQ ID No. 37). 
     
     
         15 . The method of  claim 14 , wherein the miRNA comprising the seed region sequence UCACAGU is miR_27a. 
     
     
         16 . The method of  claim 15 , wherein the miR_27a is hsa_miR_27a and comprises the nucleotide sequence set forth in SEQ ID NO:1. 
     
     
         17 . A method for decreasing the expression of VE-cadherin protein in a cell or tissue of a subject, the method comprising administering to the subject, or a cell or tissue derived therefrom, an effective amount of a miRNA comprising a seed region comprising the sequence UCACAGU (SEQ ID No. 37). 
     
     
         18 . The method of  claim 17 , wherein the miRNA comprising the seed region sequence UCACAGU is miR_27a. 
     
     
         19 . The method of  claim 18 , wherein the miR_27a is hsa_miR_27a and comprises the nucleotide sequence set forth in SEQ ID NO:1.