Antisense antibacterial compounds and methods
AssigneesBoard of Regents, The University of Texas System, Oregon State University
InventorsDavid Greenberg, Bruce L. Geller, Erdal Toprak
Life of this patent
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Abstract
Provided are antisense morpholino oligomers targeted against bacterial virulence factors such as genes that contribute to antibiotic resistance or biofilm formation, or essential genes, and related compositions and methods of using the oligomers and compositions, for instance, in the treatment of an infected mammalian subject.
Claims19
An antisense morpholino oligomer, composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′-cxocyciic carbon of an adjacent subunit, and having (a) about 10-40 nucleotide bases, and (b) a targeting sequence selected from
- a) SEQ ID NO:
- 11 (ATG TAA ACC TC);
- b) SEQ ID NO:
- 12 (GTT CAT ATG TA);
- c) SEQ ID NO:
- 13 (AAC CCT CTG TT);
- d) SEQ ID NO:
- 14 (TGT TCA TAT GT);
- wherein thymine, bases (T) may be uracil bases (U), and where the oligomer is conjugated to a cell-penetrating peptide (CPP).
A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an antisense morpholino oligomer, wherein the antisense morpholino oligomer is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′-exocyclic carbon of an adjacent subunit, and having (a) about 10-40 nucleotide bases, and (b) a targeting sequence selected from:
- a) SEQ ID NO:
- 11 (ATG TAA ACC TC);
- b) SEQ ID NO:
- 12 (GTT CAT ATG TA);
- C) SEQ ID NO:
- 13 (AAC CCT CTG TT);
- d) SEQ ID NO:
- 14 (TGT TCA TAT GT);
- wherein thymine bases (T) may he uracil bases (U), and where the oligomer is conjugated to a cell-penetrating peptide (CPP).
A method of reducing expression and activity of a virulence factor in a bacterium, comprising contacting the bacterium with an antisense morpholino oligomer, wherein the antisense morpholino oligomer is composed of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′-exocyclic carbon of an adjacent subunit, and having (a) about 10-40 nucleotide bases, and (b) a targeting sequence selected from:
- a) SEQ ID NO:
- 11 (ATG TAA ACC TC);
- b) SEQ ID NO:
- 12 (GTT CAT ATG TA);
- c) SEQ ID NO:
- 13 (AAC CCT CTG TT);
- d) SEQ ID NO:
- 14 (TGT TCA TAT GT);
- wherein thymine bases (T) may be uracil bases (U), and where the oligomer is conjugated to a cell-penetrating peptide (CPP).
Dependencies are inferred from the claim text.