Single-stranded antimicrobial oligonucleotides and uses thereof

Abstract

The current invention is directed to oligonucleotide sequences isolated from a sequence designated rbl-1 [SEQ ID NO. 19] that either kill or inhibit growth, or prevent the production of endogenously expressed toxin, of microorganisms. These ssDNA sequences, identified through use of a screening method, appear to act as modulators of essential growth functions which may act at the level of triplex formation, antisense inhibition, or as aptamers that alter gene function. The sequences, referred to as minimum functional regions, or MFRs, are useful inter alia as therapeutic agents for treatment of sepsis and other pathologies caused by microorganisms such as sepsis and/or in which microorganisms are contributory agents.

What is claimed is: 
     
         1 . A ss-ODN or ds-ODN sequence comprising a sequence of nucleotides isolated from the rbl-1 insert sequence [SEQ ID No. 19], the rbl-1 sequence [SEQ ID NO. 18], or from a sequence homologous to the rbl-1 or the rbl-1 insert sequences. 
     
     
         2 . The ss-ODN or ds-ODN sequence of  claim 1  including that portion of the sequence of rbl-1 [SEQ ID NO. 18] beginning with the nucleotides at positions ranging from positions 20-23 up to positions 32-34. 
     
     
         3 . The ss-ODN or ds-ODN sequence of  claim 1  including that portion of the sequence of rbl-1 [SEQ ID NO. 18] at positions 7-40. 
     
     
         4 . The ss-ODN or ds-ODN sequence of  claim 2  including that portion of the sequence at positions 25-31. 
     
     
         5 . The ss-ODN or ds-ODN sequence of  claim 1  wherein the sequence is between about 7 and about 15 nucleotides long. 
     
     
         6 . The ss-ODN or ds-ODN sequence of  claim 2  including that portion of the sequence of rbl-1 at positions 25-31. 
     
     
         7 . An ss-ODN or ds-ODN sequence corresponding to or homologous to the sequence of the rbl-1 insert [SEQ ID NO. 19] that functions to inhibit RNA polymerase activity when introduced into a cell. 
     
     
         8 . An expression vector including the ss-ODN or ds-ODN sequence of any of  claims 1 - 7 . 
     
     
         9 . The expression vector of  claim 8  having an inducible promoter therein. 
     
     
         10 . A cell having the expression vector of  claim 8  introduced therein.