Eligo Bioscience

Institut Pasteur

Jesus Fernandez Rodriguez

Xavier Duportet

Antoine Decrulle

David Bikard

Aymeric Leveau

Cristina Del Carmen Gil-Cruz

Christian Ivan Pérez-Shibayama

Burkhard Ludewig

Andreas Brodel

Thibault Carlier

Aurélie Mathieu

Lun Cui

Antonina Krawczyk

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.

Sequence-specific antimicrobials by blocking DNA repair

The present invention concerns nucleic acids of interest for modulating the microbiome of a host, to vectors encoding the nucleic acids and to methods for in vivo modulating the microbiome of a subject by delivering the nucleic acid of interest.

Microbiome modulation of a host by delivery of DNA payloads with minimized spread

Methods and compositions are provided for transferring a genetic circuit from one prokaryotic cell ('donor cell') to another prokaryotic cell (“recipient cell” or “target cell”). The genetic circuit contains a nucleic acid of interest under the transcriptional control of a repressor binding sequence. The nucleic acid sequence of interest may encode a protein or RNA of interest.

Transcriptional control in prokaryotic cells using DNA-binding repressors

The present invention concerns a production bacterial cell for producing lytic phage particles or lytic phage-derived delivery vehicles, said production bacterial cell stably comprising at least one phage structural genes and at least one phage DNA packaging genes, said phage structural gene(s) and phage DNA packaging gene(s) being derived from a lytic bacteriophage, wherein the expression of at least one of said phage structural genes and/or at least one of said phage DNA packaging gene(s) in said production bacterial cell is controlled by an induction mechanism.

Production of lytic phages

The present invention relates to a vector, preferably included in a delivery vehicle, comprising no more than 100, preferably no more than 10, restriction sites recognized by the restriction enzymes encoded by each bacterium of a group of bacteria of interest. The invention also relates to the use of said vector, preferably included in a delivery vehicle, as a drug, especially in the treatment of a disease in a patient in need thereof.

Optimized vector for delivery in microbial populations

The present invention concerns a production bacterial cell for producing phage particles or phage-derived delivery vehicles, said production bacterial cell stably comprising at least one phage structural gene(s) and at least one phage DNA packaging gene(s), said phage structural gene(s) and phage DNA packaging gene(s) being derived from a first type of bacteriophage,

Production bacterial cells and use thereof in production methods

The present invention relates to a vector, preferably included in a delivery vehicle, comprising no more than (100), preferably no more than (10), restriction sites recognized by the restriction enzymes encoded by each bacterium of a group of bacteria of interest. The invention also relates to the use of said vector, preferably included in a delivery vehicle, as a drug, especially in the treatment of a disease in a patient in need thereof.

The present invention concerns nucleic acids of interest for modulating the microbiome of a host, to vectors encoding the nucleic acids and to methods for in vivo modulating the microbiome of a subject by delivering the nucleic acids of interest.

The present invention concerns a production bacterial cell for producing lytic phage particles or lytic phage-derived delivery vehicles, said production bacterial cell stably comprising at least one phage structural genes and at least one phage DNA packaging genes, said phage structural gene(s) and phage DNA packaging gene(s) being derived from a lytic bacteriophage,

The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.

Modulation of microbiota function by gene therapy of the microbiome to prevent, treat or cure microbiome-associated diseases or disorders

The present disclosure relates generally to bacterial delivery vehicles for use in efficient transfer of a desired payload into a target bacterial cell. More specifically, the present disclosure relates to bacterial delivery vehicles with desired host ranges based on the presence of a chimeric receptor binding protein (RBP) composed of a fusion between the N-terminal region of a RBP derived from a lambda-like bacteriophage and the C-terminal region of a different RBP.

Chimeric receptor binding proteins for use in bacterial delivery vehicles

The present disclosure provides a chimeric receptor binding protein (RBP) resistant to proteolytic digestion wherein said RBP comprises a portion of a receptor binding protein derived from a bacteriophage fused through a designed linker region consisting of 1 to 70 amino acids, to a portion of a receptor binding protein derived from a different bacteriophage, wherein said linker region is designed to be resistant to proteolytic digestion.

Chimeric receptor binding proteins resistant to proteolytic degradation

The present disclosure relates generally to methods and compositions for transferring a genetic circuit from one prokaryotic cell ('donor cell') to another prokaryotic cell ('recipient cell' or &#x201c;target cell&#x201d; which are used interchangeably herein). More specifically, the present disclosure relates to prokaryotic donor cells comprising (i) a genetic circuit of interest and (ii) one or more expressed transcriptional repressor proteins and the use of said donor cells in the efficient transfer of the genetic circuit into a prokaryotic recipient cell. The genetic circuit includes nucleic acid sequences encoding a RNA molecule or protein of interest.

Growing community of inventors

Paris, France

Jesus Fernandez Rodriguez