METHODS OF TREATING AND PREVENTING BACTERIAL INFECTIONS
Provided herein are DNAzymes conjugated to an organic moiety and methods of facilitating entry of DNAzymes into bacteria, utilizing same. Also provided are methods of targeting bacterial target genes, methods of treating or inhibiting the progression of bacterial infections, and methods of increasing susceptibility of bacteria to an antibiotic, using the described DNAzymes, which are optionally capable of silencing at least one target gene of bacteria and/or rendering bacteria susceptible to antibiotic treatment.
1 . A method of treating a bacterial infection in a subject in need thereof, comprising administering to said subject a DNAzyme conjugated to an organic moiety, wherein said organic moiety is selected from:
a) a cyclic organic compound having multiple rings; and
b) an alkyl compound.
2 . The method of claim 1 , wherein said organic moiety is a cyclic organic compound having multiple rings, and said cyclic organic compound is a steroid.
3 . The method of claim 2 , wherein said steroid is a sterol.
4 . The method of claim 2 , wherein said steroid is a bile acid or bile alcohol.
5 . The method of claim 3 , wherein said sterol is selected from the group consisting of cholesterol, β-sitosterol, campesterol, stigmasterol, and ergosterol; and derivatives of any of aforementioned compounds with 2 or fewer substitutions.
6 . The method of claim 1 , wherein said organic moiety is an alkyl compound, and said alkyl compound is a fatty acid, comprising a chain of 8-20 carbons.
7 . The method of claim 1 , wherein said DNAzyme is conjugated to said organic moiety via a linker, and wherein said linker is an organic moiety.
8 . The method of claim 1 , wherein said DNAzyme is targeted to a transcript of a bacterial gene.
9 . The method of claim 8 , wherein said bacterial gene is an antibiotic resistance gene.
10 . The method of claim 1 , wherein said DNAzyme is a 10-23 type DNAzyme molecule.
11 . The method of claim 1 , wherein said bacterial infection is an infection with a Gram positive bacteria.
12 . The method of claim 1 , wherein said bacterial infection is an infection with a Gram negative bacteria.
13 . The method of claim 1 , wherein said bacterial infection is an infection with selected from the group consisting of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and an Enterobacter.
14 . The method of claim 1 , wherein said subject is a human subject.
15 . A method of increasing susceptibility of a bacterium to an antibiotic, in a subject having a bacterial infection, said method comprising administering to said subject a DNAzyme conjugated to an organic moiety, wherein said organic moiety is selected from:
a) a cyclic organic compound having multiple rings; and
b) an alkyl compound.
16 . The method of claim 15 , wherein said organic moiety is a cyclic organic compound having multiple rings, and said cyclic organic compound is a steroid.
17 . The method of claim 16 , wherein said steroid is a sterol.
18 . The method of claim 15 , wherein said DNAzyme is conjugated to said organic moiety via a linker, and wherein said linker is an organic moiety.
19 . The method of claim 15 , wherein said DNAzyme is targeted to a transcript of a bacterial gene.
20 . The method of claim 19 , wherein said bacterial gene is an antibiotic resistance gene.