Details for Patent: 8,314,072

Title:	Antisense antibacterial method and compound
Abstract:	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 T.sub.m of between 50.degree. to 60.degree. C. The relatively short antisense compounds are substantially more active than conventional antisense compounds having a targeting base sequence of 15 or more bases.
Inventor(s):	Geller; Bruce L. (Corvallis, OR), Deere; Jesse D. (Davis, CA), Iversen; Patrick L. (Corvallis, OR)
Assignee:	AVI BioPharma, Inc. (Corvallis, OR)
Filing Date:	Jul 01, 2005
Application Number:	11/173,847
Claims:	1. A method of inhibiting the growth of pathogenic bacterial cells, comprising exposing the bacterial cells to a growth-inhibiting amount of a substantially uncharged antisense morpholino oligomer having a sequence consisting of SEQ ID NO: 109, wherein said morpholino oligomer is composed of morpholino subunits and phosphorodiamidate intersubunit linkages joining a morpholino nitrogen of one subunit to a 5' exocyclic carbon of an adjacent subunit. 2. The method of claim 1, wherein the morpholino subunits in the morpholino oligomer to which the cells are exposed are joined by phosphorodiamidate linkages, in accordance with the structure: ##STR00003## where Y.sub.1=O, Z=O, Pj is a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide, and X is alkyl, alkoxy, thioalkoxy, amino, or --NR.sub.2, where each R is independently hydrogen or methyl. 3. The method of claim 1, for use in inhibiting a bacterial infection in a mammalian subject, wherein said exposing includes administering said morpholino oligomer in a therapeutically effective amount. 4. The method of claim 3, which further includes treating the subject by administration of a non-antisense compound having antibacterial activity. 5. The method of claim 1, wherein the morpholino subunits in the oligonucleotide compound are joined by phosphorodiamidate linkages, in accordance with the structure: ##STR00004## where Y.sub.1=O, Z=O, Pj is a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide, and X is alkyl, alkoxy, thioalkoxy, amino, alkyl amino, dialkylamino, or 1-piperazinyl, wherein X is 1-piperazinyl in at least one linkage and up to about 1 of every 5 linkages.