Patent ID: 8067571

Claim:
A method for enhancing the antibacterial activity of an uncharged 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, where the oligonucleotide contains between 10-20 bases and a targeting sequence of at least 10 contiguous bases complementary to a bacterial RNA target, and where binding of the oligonucleotide to the RNA target region is effective to inhibit growth of a infectious bacterium in a mammalian host, comprising both of steps (a) and (b), or step (b) alone: (a) conjugating to the oligonucleotide, a carrier peptide (i) containing 8-14 amino acids composed of the subsequences selected from the group represented by XXY, XY, XZZ, XZ, XYX, YXX, YX, ZXZ, ZZX, and ZX, where (a) each X subunit independently represents arginine or an arginine analog, said analog being a cationic α-amino acid comprising a side chain of the structure R 1 N═C(NH 2 )R 2 , where R 1 is H or R; R 2 is R, NH 2 , NHR, or NR 2 , where R is lower alkyl or lower alkenyl and may further include oxygen or nitrogen; R 1 and R 2 may together form a ring; and the side chain is linked to said amino acid via R 1 or R 2 ; (b) each Y subunit independently represents a neutral linear amino acid —C(O)—(CHR)m-NH—, where (i) m is 1 to 7 and each R is independently H or methyl, and (c) Z is an α-amino acid having a neutral side chain selected from a substituted or unsubstituted aralkyl, and (ii) coupled to the oligonucleotide at the peptide's C terminus, and (b) modifying the oligonucleotide to contain at least one and up to 50% intersubunit linkages comprising an optionally substituted piperazino group.