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AssigneesInstitut Pasteur, Eligo Bioscience
InventorsDavid Bikard, Lun Cui, Xavier Duportet, Jesus Fernandez Rodriguez
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The invention relates to the improvement of endonuclease-based antimicrobials by blocking DNA repair of double-strand break(s) (DSB(s)) in prokaryotic cells. In this respect, the invention especially concerns a method involving blocking DNA repair after a nucleic acid has been submitted to DSB, in particular by a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated programmable double-strand endonuclease. The invention particularly relates to the use of an exogenous molecule that inhibits DNA repair, preferably a protein that binds to the ends of the double-stranded break to block DSB repair. The invention also relates to vectors, particularly phagemids and plasmids, comprising nucleic acids encoding nucleases and Gam proteins, and a pharmaceutical composition and a product containing these vectors and their application.
A method for killing a bacterium comprising contacting the bacterium with at least one recombinant phagemid(s) or plasmid(s);
A method for making a bacterium more susceptible to an antibiotic comprising contacting the bacterium with at least one recombinant phagemid(s) or plasmid(s) and the antibiotic;
A phagemid or plasmid vector encoding an endonuclease selected from a meganuclease, a Zinc Finger Nuclease, and a TALEN, and an exogenous protein inhibiting DSB repair selected from the group consisting of Mu phage Gam protein, a lambda phage Gam protein, a phage T7 gp5.9 protein.
Dependencies are inferred from the claim text.