Methods and composition for inhibition of tRNA activities
AssigneeThomas Jefferson University
InventorYa-Ming Hou
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Abstract
A method of inhibiting activities of a tRNA of a selected pathogen is provided wherein a cell infected with a selected pathogen is contacted with an effective amount of an oligonucleotide targeted to a region of the cloverleaf structure of a tRNA of the selected pathogen. Compositions for inhibiting activities of a tRNA of a selected pathogen which contain an oligonucleotide targeted to a region of cloverleaf structure of a tRNA of the selected pathogen are also provided. In addition, methods of killing the pathogen with these compositions are provided.
Claims24
A composition which inhibits activities of a tRNA comprising an oligonucleotide which is fully complementary to a sequence set forth in SEQ ID NO:1, 2, 4, 5, 6, 9 or 10.
A composition comprising an oligonucleotide, wherein the oligonucleotide is fully complementary to a target selected from the group consisting of:
- (a) a sequence consisting of nucleotides set forth in SEQ ID NO.:1;
- (b) a sequence consisting of nucleotides set forth in SEQ ID NO.:2;
- (c) a sequence consisting of nucleotides set forth in SEQ ID NO.:4;
- (d) a sequence consisting of nucleotides set forth in SEQ ID NO.:5;
- (e) a sequence consisting of nucleotides set forth in SEQ ID NO.:6;
- (f) a sequence consisting of nucleotides set forth in SEQ ID NO.:9;
- and
- (g) a sequence consisting of nucleotides set forth in SEQ ID NO.:10;
- wherein the oligonucleotide inhibits the ability of a tRNA to be aminoacylated by a cognate tRNA synthetase in a cell.
A 2′-O-alkyl oligonucleotide targeted to a region consisting of or adjacent to one or more cognate tRNA synthetase recognition nucleotides of a cloverleaf structure of a tRNACys of E. coli or H. influenzae, wherein the oligonucleotide is fully complementary to a sequence set forth in SEQ ID NO:
- 4.
A 2′-O-alkyl oligonucleotide targeted to a region consisting of or adjacent to one or more cognate tRNA synthetase recognition nucleotides of a cloverleaf structure of a tRNACys of E. coli or H. influenzae, wherein the oligonucleotide is fully complementary to a sequence set forth in SEQ ID NO:
- 5.
A 2′-O-alkyl oligonucleotide targeted to a region consisting of or adjacent to one or more cognate tRNA synthetase recognition nucleotides of a cloverleaf structure of a tRNACys of E. coli or H. influenzae, wherein the oligonucleotide is fully complementary to a sequence set forth in SEQ ID NO:
- 6.
A method of inhibiting activities of a tRNA of a bacterium comprising contacting the bacterium with an oligonucleotide which is fully complementary to a sequence set forth in SEQ ID NO:
- 1, 2, 4, 5, 6, 9 or 10 that is targeted to a region of a cloverleaf structure of the tRNA such that activities of the tRNA are inhibited wherein the bacterium is E. coli or Hinfluenzae.
A method of inhibiting aminoacylation of a cloverleaf structure of a tRNA in a bacterial cell comprising contacting the bacterial cell with 2′-O-alkyl oligonucleotide which is fully complementary to a sequence set forth in SEQ ID NO1, SEQ ID NO:2, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 9, or SEQ ID NO 10 such that aminoacylation of the cloverleaf structure of the tRNA is inhibited, wherein the bacterial cell is E. coli or H. influenzae.
Dependencies are inferred from the claim text.