Methods and compositions to prevent microbial infection
Inventors
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Assignees
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Commense BioCommense Bio is a biopharmaceutical company focusing on developing genetically engineered bacterial therapeutics for invasive infections. With a proprietary technology platform, the company is advancing live biotherapeutic products (LBPs) addressing various infectious diseases including MRSA, recurrent UTIs, cystic fibrosis-associated infections, and more. Their innovations center around gene-edited bacteria and microbiome substitution—with a single, prescription-only application administered dermally or nasally—as a novel, non-antibiotic approach against antimicrobial resistance. The team includes experience in drug development, commercialization, and scientific research.
Commense Bio is a biopharmaceutical company focusing on developing genetically engineered bacterial therapeutics for invasive infections. With a proprietary technology platform, the company is advancing live biotherapeutic products (LBPs) addressing various infectious diseases including MRSA, recurrent UTIs, cystic fibrosis-associated infections, and more. Their innovations center around gene-edited bacteria and microbiome substitution—with a single, prescription-only application administered dermally or nasally—as a novel, non-antibiotic approach against antimicrobial resistance. The team includes experience in drug development, commercialization, and scientific research.
Publication Number
US-12163135-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Methods and compositions are provided for durably influencing microbiological ecosystems (microbiomes) in a subject in order to prevent infection and reduce recurrence of infection by microorganisms. In some embodiments, compositions and methods are provided for the creation and use of molecularly-modified bacterial strains with the potential to prevent a variety of microorganism infections.
Core Innovation
The invention relates to a synthetic microorganism comprising a recombinant nucleotide with at least one kill switch molecular modification integrated into a chromosome. The synthetic microorganism is derived from a Staphylococcus aureus strain and includes a first cell death gene operatively associated with a first regulatory region comprising an inducible first promoter.
The inducible first promoter exhibits conditionally high level gene expression in response to exposure to blood, serum, or plasma, with the expression increase specified as at least three fold above basal productivity. This increase is determined before and from 30 minutes to 180 minutes after exposure by quantitative polymerase chain reaction (qPCR) or RNA sequencing (RNAseq).
The first cell death gene comprises an sprA1 gene comprising the nucleotide sequence of SEQ ID NO: 284. The disclosure also describes a genomic serum-responsive kill-switch cassette and genomic integration of a Ptetr-gfp reporter to demonstrate controllable inducible expression from the chromosome.
Claims Coverage
The independent claim covers a chromosomally integrated kill switch in a Staphylococcus aureus-derived synthetic organism. It includes three inventive features centered on an sprA1 cell death gene controlled by an inducible promoter responsive to blood, serum, or plasma with a defined at least three fold increase over basal productivity measured by qPCR or RNAseq within 30 to 180 minutes.
Chromosomally integrated kill switch in a Staphylococcus aureus-derived synthetic organism
The synthetic microorganism is derived from a Staphylococcus aureus strain, and the at least one kill switch molecular modification is integrated to a chromosome of the synthetic microorganism.
Inducible first promoter responsive to blood, serum, or plasma
A first regulatory region comprising an inducible first promoter conditionally drives gene expression in response to exposure to blood, serum, or plasma, with an expression increase of at least three fold over basal productivity as determined before and from 30 minutes to 180 minutes after exposure by qPCR or RNA sequencing (RNAseq).
sprA1 cell death gene
The first cell death gene comprises an sprA1 gene comprising the nucleotide sequence of SEQ ID NO: 284.
Overall, the claim set centers on a Staphylococcus aureus-derived synthetic organism carrying a chromosomally integrated kill switch in which an sprA1 cell death gene is placed under an inducible promoter that responds to blood, serum, or plasma with a defined at least three fold expression increase measured by qPCR or RNAseq within 30 to 180 minutes.
Stated Advantages
Durably replacing an undesirable microorganism in a dermal/mucosal niche while preventing recurrent infection.
Providing non-co-colonization and supporting microbiome resilience as a basis for durability.
Conditionally high level gene expression in response to exposure to blood, serum, or plasma as determined by qPCR or RNA sequencing.
The inducible promoter exhibits at least three fold increase of basal productivity within 30 minutes to 180 minutes after exposure to blood, serum, or plasma.
A constructed genomic serum-responsive kill-switch cassette yields a ~97.39% reduction in viable cells after 3 hours in human serum while maintaining growth in TSB.
Documented Applications
Preventing or reducing recurrence of infection by suppressing an undesirable microorganism and durably replacing it with a synthetic microorganism occupying the same dermal/mucosal niche.
Use in a serum-responsive kill-switch context to reduce viable cells after exposure to human serum while maintaining growth in TSB.
Use of a pharmaceutical composition comprising an effective amount of the synthetic microorganism together with one or more pharmaceutically acceptable formulation components.
Clinical study background/results on MRSA suppression/recolonization durability using BioPlx-01WT versus decolonization-only controls are described.
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