Antibacterial antisense oligonucleotide and method
AssigneeSarepta Therapeutics, Inc.
InventorsDwight D. Weller, Bruce L. Geller, Patrick L. Iversen, Lucas D. Tilley, Jed N. Hassinger
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Abstract
A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
Claims13
An antisense conjugate, comprising
- (a) an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, wherein the oligonucleotide contains between 10-20 bases and a targeting sequence of at least 10 contiguous bases complementary to a target sequence containing or within 20 bases, in a downstream direction, of the translational start codon of a bacterial mRNA that encodes acyl carrier protein (acpP), wherein the target sequence is the Burkholderia mallei acpP sequence of SEQ ID NO:
- 54 or the Burkholderia pseudomallei acpP sequence of SEQ ID NO:
- 57, and
- (b) a carrier peptide represented by the formula (RAhxR)4 or (RFF)3, wherein Ahx is aminohexanoic acid.
Dependencies are inferred from the claim text.