Multivalent aptamer complexes

Abstract

A compound of the formula A-B-C, is provided, wherein: A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest, B is an alkyl linker; and C is a second nucleic acid that hybridizes to a complementary nucleic acid. In some embodiments, the first nucleic acid is an aptamer. In some embodiments, the nucleic acid comprises an active compound, particularly cytotoxic nucleotides such as poly-FdUMP. Compositions and methods of using such compounds for treating and/or detecting cancer are also described.

That which is claimed is: 
     
         1 . A compound of the formula A-B-C, wherein:
 A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest,   B is an alkyl linker; and   C is a second nucleic acid that hybridizes to a complementary nucleic acid.   
     
     
         2 . The compound of  claim 1 , wherein said first nucleic acid is an aptamer. 
     
     
         3 . The compound of  claim 1 , wherein said first nucleic acid is from 30 to 150 nucleotides in length. 
     
     
         4 . The compound of  claim 1 , wherein said first nucleic acid is selected from the group consisting of DNA and RNA. 
     
     
         5 . The compound of  claim 1 , wherein said first nucleic acid is a DNA having the sequence of PSMA01: 
       
         
           
                 
               
                   (SEQ ID NO: 1) 
                 
                   5′-dGCGTTTTCGCTTTTGCGTTTTGGGTCATCTGCTTACGATAGCAATC 
                 
                     
                 
                   GT. 
                 
             
                
                
                
                
               
            
           
         
       
     
     
         6 . The compound of  claim 1 , wherein said alkyl linker comprises C2-C6 loweralkyl. 
     
     
         7 . The compound of  claim 1 , wherein said second nucleic acid is from 8 to 100 nucleotides in length. 
     
     
         8 . The compound of  claim 1 , wherein said second nucleic acid is selected from the group consisting of DNA and RNA. 
     
     
         9 . The compound of  claim 1 , wherein said cell of interest is a cancer cell. 
     
     
         10 . The compound of  claim 1 , wherein said cell of interest is a microbial cell. 
     
     
         11 . The compound of  claim 1 , wherein said cell of interest is a parasitic cell. 
     
     
         12 . The compound of  claim 1 , wherein said nucleic acid comprises an active compound. 
     
     
         13 . The compound of  claim 1 , wherein said nucleic acid comprises a detectable group. 
     
     
         14 . The compound of  claim 1 , wherein said nucleic acid comprises more than one active compound and/or detectable group. 
     
     
         15 . The compound of  claim 12 , wherein said active compound comprises cytotoxic nucleotides. 
     
     
         16 . The compound of  claim 15 , wherein said cytotoxic nucleotides comprise poly-FdUMP. 
     
     
         17 . The compound of  claim 1 , wherein said extracellular surface protein is an extracellular surface protein differentially expressed by cancer cells. 
     
     
         18 . The compound of  claim 17 , wherein said extracellular surface protein comprises an extracellular surface portion of prostate specific membrane antigen (PSMA). 
     
     
         19 . A composition comprising a pair of compounds of  claim 1 , each member of said pair having a second nucleic acid that is complementary to and hybridized to the second nucleic acid of the other member of said pair. 
     
     
         20 . The composition of  claim 19  in a pharmaceutically acceptable carrier. 
     
     
         21 . A method of introducing a nucleic acid of interest into a cell of interest, comprising contacting a composition of  claim 19  to said cell under conditions in which said nucleic acid of interest is internalized into said cell. 
     
     
         22 . The method of  claim 21 , wherein said method is carried out in vitro. 
     
     
         23 . The method of  claim 21 , wherein said method is carried out in vivo. 
     
     
         24 . The method of  claim 21 , wherein said cell of interest is a cancer cell in a subject afflicted with cancer, and said contacting is carried out by administering said composition to said subject in an amount effective to treat or detect said cancer. 
     
     
         25 . The method of  claim 25 , wherein said cancer is prostate cancer.