University of Texas System

Oregon State University

Sarepta Therapeutics, Inc.

Avi Biopharma, Inc.

Bruce L Geller

Patrick L Iversen

David Greenberg

Dwight D Weller

Lucas D Tilley

Jed N Hassinger

Jesse D Deere

Erdal Toprak

Jesse D Center For Comparative Medicine Deere

Provided are antisense oligomers targeted against bacterial mRNAs and other macromolecules associated with a biochemical pathway and/or cellular process, and related compositions and methods of using the oligomers and compositions to treat an infected mammalian subject, for example, as primary antimicrobials or as adjunctive therapies with classic antimicrobials.

Antisense antibacterial compounds and methods

Provided are antisense oligonucleotides targeted against bacterial genes involved in biochemical pathways and/or cellular processes, and related compositions and methods of using the oligonucleotides and compositions, alone or in combination with other antimicrobial agents, for instance, in the treatment of an infected mammalian subject.

Provided are antisense morpholino oligomers targeted against bacterial virulence factors such as genes that contribute to antibiotic resistance or biofilm formation, or genes associated with fatty acid biosynthesis, and related compositions and methods of using the oligomers and compositions, for instance, in the treatment of an infected mammalian subject.

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.

Provided are antisense oligomers targeted against or genes associated with a biochemical pathway and/or cellular process, and related compositions and methods of using the oligomers and compositions to treat an infected mammalian subject, for example, as primary antimicrobials or as adjunctive therapies with classic antimicrobials.

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

A method and antisense compound for inhibiting the growth of pathogenic bacterial cells are disclosed. The compound contains no more than 12 nucleotide bases and has a targeting nucleic acid sequence of no fewer than 10 bases in length that is 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. The compound binds to a target mRNA with a Tof between 50&#xb0; to 60&#xb0; C. The relatively short antisense compounds are substantially more active than conventional antisense compounds having a targeting base sequence of 15 or more bases.

Antisense antibacterial method and compound

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.

Growing community of inventors

Corvallis, OR, United States of America

Bruce L Geller