Antisense oligonucleotides and ceftriaxone in the strategy against resistances to antibiotics: laso system

The present invention relates to the treatment of infections due to antibiotic-resistant bacteria. Antimicrobial resistance (AMR) has been observed at dangerously high levels worldwide and alternative strategies are urgently needed. Antisense therapy has been identified as potential therapeutic tool for tackling AMR. However, in the context of AMR, since the antisense oligonucleotides have to reach the target mRNA to be efficient, the cellular uptake inside prokaryotic cells is a critical issue. The inventors demonstrated that antisense oligonucleotide sequences, in particular targeting the blaCTX/M15 gene, featuring a lipid moiety conjugated to the ASO extremity show a particularly efficient intracellular penetration in prokaryotic cells and that these lipid-modified antisense oligonucleotides can show a further improved enzymatic stability with phosphorothioate chemistry (PTO). In particular, the present invention relates to an antisense oligonucleotide modified by substitution at the 5’ or the 3’ end by a lipid moiety, wherein said antisense oligonucleotide specifically targets an mRNA encoding a CTX-M extended spectrum β-lactamase. Another object of the invention concerns the antisense oligonucleotide of the invention for use for treating a bacterial infection, in particular due to bacteria resistant to 3rd generation cephalosporins.

Keywords: Biologic;Infectious Diseases;Nucleic acids;Product ;Therapeutic, antibiotic-resistant bacteria, ASO
Patent Application number: European Procedure (Patents) (EPA) - 09 Mai 2019 - 19305585.2
Inventors:
KAUSS Tina,ARPIN Corinne,BARTHELEMY Philippe,NGUYEN Phuoc Vinh

Reference:

BIO18250-T1

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