Sarepta Therapeutics, Inc.

Avi Biopharma, Inc.

Lucas D Tilley

Patrick L Iversen

Bruce L Geller

Dwight D Weller

Jed N Hassinger

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&#x2032; 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.

Antibacterial antisense oligonucleotide and method

An antibacterial antisense conjugate and method of using the same for treating a bacterial infection in a mammalian host are disclosed. The conjugate includes an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotide contains 10-20 nucleotide bases and has a targeting nucleic acid sequence complementary to a target sequence containing or within 10 bases, in a downstream direction, of the translational start codon of a bacterial mRNA that encodes a bacterial protein essential for bacterial replication, where the compound binds to a target mRNA with a Tof between 50&#xb0; to 60&#xb0; C. The carrier peptide is an arginine-rich peptide containing between 6 and 12 amino acids.

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Burlington, VT, United States of America

Lucas D Tilley