Design of Engineered Therapeutic Strains
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With the development of efficient DNA techniques for manipulating microbial genomes and increasing knowledge of the molecular basis of disease, it is possible to design bacteria specifically to treat human diseases. A new live biotherapeutics consisting of engineered microbes could tackle specific mechanisms of disease. Engineered bacterial strains can be designed to sense and respond to environmental signals within the body, including those in the gastrointestinal tumor tract or the microenvironment of solids. Creative Biolabs is a complete live biotherapeutic product (LBP) solutions provider, we deliver therapeutic strains engineering services of unparalleled quality.
Synthetic Biology Approaches Improving Bacterial Therapies
Synthetic biology aims to rationally design bacteria for therapeutic and other applications by developing computational tools and techniques for extreme genetic manipulation. Through these methods, designed biological modules, devices, and regulatory circuits for predictable behavior can be integrated into the bacterial chassis genome through strict biological control measures. Ideally, engineered bacteria for treatment should be sensitive to antibiotics and free of mobile elements such as transposons and plasmids. In addition, engineered bacteria must have their containment strategies to resist environmental replenishment, mutagenesis drift, and horizontal gene transfer.
Engineered Therapeutic Strains Construction Services
Many studies have linked dysbiosis to diseases such as infections, inflammation, allergy, asthma, obesity, cancer, and even neurological disorders. Therefore, targeting the microbiome with specific microorganisms will help develop therapies for such diseases. These intentional administrations with natural bacteria have been mostly performed with strains of lactic acid bacteria (e.g. Lactobacillus, Bifidobacterium) but also with Escherichia coli strains, such as E. coli Nissle 1917.
Advantages
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Genetic engineering can confer functions that the endogenous microbiota does not express.
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Engineering LBP can be designed to execute natural biological processes.
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The functions encoded by engineering bacteria also have the potential to treat congenital metabolic errors.
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Targeted therapy delivery.
Applications of Engineered Bacteria
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Against Inflammatory and Autoimmune Disorders
Different bacteria have been engineered to express a wide variety of compounds (such as antioxidant enzymes, and anti-inflammatory cytokines) in situ. A strain of Lactococcus lactis engineered to secrete the anti-inflammatory cytokine IL-10 has shown clinical benefit in patients with Crohn's disease. Another Lactococcus lactisstrain, which expresses human Trefoil Factor 1 (hTFF1), has been made into a mouthwash for the treatment of oral mucositis.
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Against Cancer
Engineered bacteria induce the immune system to fight tumor cells by in-situ delivery of pro-apoptotic peptides, anti-angiogenic factors, and cytokines, thus competing with mechanisms that promote tumor formation. Bacteria are also designed to silence the expression of important genes related to tumor development through RNA interference.
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For the Treatment of Metabolic Disorders
A strain of engineered Lactobacillus gasseri strain that secretes GLP-1 has been able to reprogram intestinal cells into insulin-secreting cells. Engineering bacteria have also been used to reduce elevated blood glucose levels (hyperglycemia) in T1D patients.
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To Combat Viral and Bacterial Infections
Strains of Lactococcus lactis and Escherichia coli have been modified to secrete different bacteriocins that respond to multiresistant E. faecalis pheromones and Pseudomonas aeruginosa quorum sensing molecules, respectively, showing bactericidal activity in vitro. An engineered strain of Lactobacillus casei secreting human lactoferrin was shown to be effective in reducing the load of pathogenic E. coli in the duodenal fluid of infected mice. Lactobacillus jensenii, part of the normal human vaginal flora, is engineered to secrete cyanovirin-N, a cyanobacterial protein with antiviral activity.
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Synthetic biology provides modular parts and gene circuits that can be used to program the designed bacterial chassis to precisely control the expression and delivery of therapeutic proteins, and the adhesion of the engineered bacteria to target cells or modify their chemotactic behavior. Creative Biolabs is a USA biotech company. We have specialized in providing custom LBP development services for researchers around the world. Our experts can help you from the very first idea, by providing expert consultancy in the design of your study. We are happy to discuss your objectives. If you are interested in our services and products, please contact us for more details.
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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