Engineering Clostridium butyricum Services for Live Biotherapeutics Drug Discovery
Background Services Advantages FAQs Published Data Resources
Background
Clostridium butyricum belongs to Bacillus. Currently, Clostridium butyricum is rarely designed for healthcare and disease prevention but is mainly used for biosynthesis. Most of these studies involve modifying metabolic pathways to optimize production through gene overexpression or inactivation. It can also serve as an adjunct to current treatments, and advances in synthetic biology tools for Clostridium have played a key role in the development of Clostridium-based biotherapy (CBT). Oral spores encapsulated with prebiotics have also been reported to specifically enrich and inhibit colon cancer, regulating gut microbiota. Genetic manipulation of tumor-producing Clostridium sporogenes or probiotic Clostridium butyricum can produce bioactive interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), porcine epidermal growth factor (pEGF), and glucagon-like peptide-1 (GLP-1). Clostridium butyricum, a probiotic with strong gastrointestinal passage ability and butyric acid secretion, has been used in preclinical treatment of hypertension associated with obstructive sleep apnea.
In general, to perform gene editing in Clostridium butyricum (CB), a plasmid system that shuttles and replicates in E. coli and Clostridium butyricum is first required. Many plasmids have been successfully applied to Clostridium, including pMTL007 and pMTL82151 plasmids. Recently, highly efficient gene editing tools developed in Clostridium butyricum using exogenous type II gene editing systems and endogenous type I-B gene editing systems have also been reported. This easy-to-apply technique lays the foundation for CB-based treatments. In addition, CB-OMVs are highly productive and can stimulate the innate immune system, suggesting that CB-OMVs also have the potential to act as a vector to deliver antigens or carry therapeutic factors through genetic manipulation.
Engineering Clostridium butyricum Services
Services
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Gene knock-out
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Gene knock-in/Gene insertion
Deliverables
Engineered strains in glycerol stock
Quality Control
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Sequencing Validation
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Western Blot Validation (Optional)
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PAGE
or cell-based assay of your interest.
Delivery Time
Starting from 4-6 weeks.
Materials from Clients
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Overall construction scheme.
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Host strain.
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Target gene name.
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Target gene sequence. (If the whole genome sequence is unavailable.)
How Clostridium butyricum Strain Construction Service Can Assist Your Project
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Construct the target strains according to the needs of clients or referring to the published scheme.
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Optimize the program to improve the success rate.
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Delivery of the constructed target strains (knockout or integrated).
Advantages
Using Clostridium butyricum as a chassis for genetic engineering modification has several advantages:
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Spore-forming capability
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Butyrate production
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Metabolic flexibility
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Probiotic benefits
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Genetic tools availability
Frequently Asked Questions
Can Clostridium butyricum strains be genetically modified?
Yes,
Clostridium butyricum strains can indeed be genetically modified. Researchers have been studying various methods to genetically modify bacteria for different applications. Here are some commonly used techniques:
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Electrotransformation: This method involves applying an electric field to bacterial cells to introduce DNA. It has been successfully used for gene transfer in Clostridium butyricum.
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Plasmid-Based Transformation: This technique uses plasmids (small, circular DNA molecules) to carry and deliver desired genes into the bacterium, enabling it to express new traits.
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Multiplex Genome Editing: Advanced methods, such as gene-editing systems, have been developed to perform precise and simultaneous modifications of multiple genes within the bacterial genome.
These genetic modifications enable
Clostridium butyricum to be tailored for various purposes, such as enhancing its probiotic properties, producing biofuels, or generating therapeutic proteins.
What are the reported Clostridium butyricum strains that have been genetically modified?
Several genetically engineered strains of
Clostridium butyricum have been reported:
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Clostridium butyricum with NY-ESO-1 expression: This strain has been engineered to express the NY-ESO-1 antigen, which is a promising cancer vaccine candidate.1, 3
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Clostridium butyricum with SARS-CoV-2 Spike_S1 antigens: This strain has been modified to produce and secrete SARS-CoV-2 Spike_S1 antigens, aiming to develop an oral vaccine against COVID-19.1, 3
These modifications demonstrate the potential of
Clostridium butyricum in therapeutic applications, including cancer treatment and vaccine development.
Published Data
Engineered probiotics Clostridium butyricum-pMTL007-GLP-1 improves blood pressure via producing GLP-1 and modulating gut microbiota in spontaneous hypertension rat models2, 3
Abstract
Researchers constructed an engineered bacterium capable of secreting GLP-1 and butyric acid, Clostridium butyricum GLP-1, and treated spontaneously hypertensive rats (SHR) with oral probiotic suspension. The heart-improvement effect of the engineered probiotic strain on hypertension was evaluated. The results showed that CB-GLP-1 gene-engineered bacteria had a good antihypertensive effect on SHR type hypertensive rat model. The findings suggest that genetically engineered bacteria expressing GLP-1 and short-chain fatty acids may be drugs to treat high blood pressure.
Fig.2 The underlying mechanism of therapeutic effect of CB-GLP-1.2, 3
Resources
Creative Biolabs is a full-service probiotic contract research organization (CRO) that supports multiple research directions in probiotics, and we have the advantage of being able to combine our technology platforms and expert team to provide flexible solutions according to the individual needs of our customers. Are you thinking about a particular application or project involving Clostridium butyricum? Please feel free to contact us for more details.
References
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Zhang, Yanchao, et al. "Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination." Microbial cell factories 23.1 (2024): 119.
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Wang, Xin‐liang, et al. "Engineered probiotics Clostridium butyricum‐pMTL007‐GLP‐1 improves blood pressure via producing GLP‐1 and modulating gut microbiota in spontaneous hypertension rat models." Microbial Biotechnology 16.4 (2023): 799-812.
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Distributed under Open Access license CC BY 4.0, without modification.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
