Engineered Escherichia coli Nissle 1917 for Disease-targeting Therapy
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Characteristics of Escherichia coli Nissle 1917 (EcN)
EcN has been used as a probiotic since its isolation. EcN has two small cryptic plasmids called pMUT1 and pMUT2. Both plasmids were fully sequenced, genetically stable, and non-transferable, and found only in EcNs. EcN has been used to treat a variety of gastrointestinal diseases without engineering. In recent years, ongoing research has focused on the genetic manipulation of EcN, using EcN as a vector for the treatment of obesity, diabetes, intestinal diseases, and other diseases. Another advantage of EcN as a chassis organism for engineered biotherapy is its wealth of knowledge on transcriptional and translational control of gene expression in Escherichia coli strains.
Engineering EcN-based Therapeutics
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Enhancing the Antimicrobial Properties of EcN
The development of EcN-based therapeutics targets the killing of gastrointestinal bacterial pathogens by generating variants to secrete antimicrobial proteins into the intestinal lumen. The overall strategy has been to outfit EcN to release bacteriocins, ribosomally synthesized secreted antimicrobial proteins that inhibit the growth of related bacterial species. Recombinant EcN-cqsA inhibited the expression of cholera toxin (CT) and toxin coregulated pilus (TCP) in Vibrio cholerae monoculture and co-culture of epithelial cells with Vibrio cholerae. Human α-defensin 5 (HD5) and β-defensin 2 (HBD2) have also been expressed from EcN and HBD2 was shown to have antimicrobial activity. EcN has also been modified to express omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may have beneficial effects on human health.
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Engineering EcN for the Treatment of IBDs
To enhance its therapeutic efficacy, researchers recently sought to enhance its ability to promote intestinal mucosal healing by engineering EcN to produce molecules naturally involved in this process. EcN was used to express interleukin-10 (IL-10) and is effective in inflammatory bowel disease (IBD) mouse models.
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Rewiring EcN for the Processing of Toxic Metabolites
EcN-based therapeutics are emerging as a platform for the treatment of diseases associated with the accumulation of toxic metabolites.
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Engineering EcN for the Treatment of Cancer
There are three main strategies for EcN-based cancer therapy: (1) specific tumor delivery of drugs or nanoparticles as microrobots, (2) design EcN to express anticancer proteins for tumor management, and (3) deliver immunomodulators for cancer immunotherapy.
Complete genomic DNA sequences provide a powerful impetus for EcN engineering approaches. Engineered microbes are rapidly evolving to deliver therapeutic modalities to disease sites. EcN, a genetically controlled probiotic with a good human safety record, is becoming a popular chassis.
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Express Direct Therapeutic Factors
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Express Adjuvant Therapeutic Factors
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EcN or EcN-derivatives as a Targeted Delivery System of Therapeutic Factors
Case Studies
Case 1: Gene Knock-out and Knock-in in Escherichia coli Nissle 1917 Strain
Objective: Based on the client's gene information and engineering strain construction requirements, construct engineering strains.
Results: Verified by PCR and sequencing, the knock-in and knock-out strains of E. coli Nissle 1917 have been correctly constructed.
Method: gene editing mediated knock-in and knock-out.
Turnaround time: 8-10 weeks.
Deliverable:
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Strains
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E. coli Nissle 1917 strains, 1.5 mL/vial, 2 vials.
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EcN knock-out strains, 1.5 mL/vial, 2 vials.
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EcN knock-in strains, 1.5 mL/vial, 2 vials.
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Project report
Including detailed materials and methods, PCR validation results, and sequencing results.
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Creative Biolabs' team is made up of highly dedicated scientists, experienced managers, and talented commercial developers, each of whom is committed to helping our partners and customers leap forward and lead progress in the life sciences. If you are interested in our genetically modified services for EcN, please feel free to contact us for more.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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