Nucleic acid complexes
The present invention relates to complexes of transcription factor decoys, their delivery to bacteria and their formulation. In particular, the present invention resides in an antibacterial complex comprising a nucleic acid sequence and one or more delivery moieties selected from quaternary amine compounds; bis-aminoalkanes and unsaturated derivatives thereof, wherein the amino component of the aminoalkane is an amino group forming part of a heterocyclic ring; and an antibacterial peptide.
1. An antibacterial complex comprising:
a double stranded nucleic acid sequence comprising the sequence of a native cellular binding site for a bacterial transcription factor; and
one or more delivery moieties represented by the formula:
wherein:
A is a bond;
p and q are the same or different and each is an integer from 1 to 12; provided that the sum of p and q is in the range from 8 to 18;
R 8 and R 8a are each selected from hydrogen; C 1-4 alkoxy; nitro; amino; mono- and di-C 1-4 alkylamino; and guanidinyl;
R 9 is hydrogen;
R 9a is hydrogen;
R 10 is selected from hydrogen; amino; and C 1-4 alkyl optionally substituted with one or more fluorine atoms;
R 10a is selected from hydrogen; amino; and C 1-4 alkyl optionally substituted with one or more fluorine atoms;
or R 9 and R 10 link together to form an alkylene chain (CH 2 ) w wherein w is 3 to 5: and/or
R 9a and R 10a link together to form an alkylene chain (CH 2 ) w wherein w is 3 to 5 provided that the compound of the formula is other than dequalinium,
wherein the nucleic acid sequence is complexed with the one or more delivery moieties.
2. The antibacterial complex of claim 1 , wherein the native cellular binding site comprises the sequence of a bacterial SigB binding site.
3. The antibacterial complex according to claim 2 , wherein the bacterial SigB binding site is represented by SEQ ID NOS: 9, 10, 30 and 31, 39, 40 or 41.
4. The antibacterial complex of claim 1 , wherein the native cellular binding site comprises the sequence of a bacterial Fur binding site.
5. The antibacterial complex of claim 4 , wherein the bacterial Fur binding site is represented by SEQ ID NOS: 11, 12 or 13.
6. The antibacterial complex of claim 1 , wherein the bacterial infection is methicillin resistant.
7. The antibacterial complex of claim 1 , wherein the bacterial infection causes sepsis.
8. The antibacterial complex of claim 7 , wherein the native cellular binding site comprises SEQ ID NO: 9.
9. The antibacterial complex of claim 1 , wherein the alkyl chain has 12 or 14 methyl groups.
10. The antibacterial complex of claim 9 , wherein the delivery moiety has the formula: