Engineering Clostridium spp. Services for Live Biotherapeutics Drug Discovery

Background Services Tools Advantages FAQs Resources

Background

Micrographs of C.novyi spores and outgrowth.

As an important part of the gut microbiota, Clostridium actively interacts with host organisms and makes a significant contribution to human health. Clostridium has demonstrated potential to treat cancer, and a new attenuated strain of Clostridium and an obligate anaerobic Clostridium are a major advance in using the bacteria to target tumors. Clostridium-directed enzyme prodrug therapy has also emerged as a promising strategy. Clostridium-mediated cancer immunotherapy, the innovative approach of genetically engineering Clostridium to produce cytokines or antibodies, has further expanded the therapeutic potential of Clostridium in cancer treatment. In addition to oncology, the scope of research on symbiotic Clostridium has expanded to include the exploration of microbe-host interactions and biomedical applications.

Engineering Clostridium spp. Services

Gene-editing Systems for Clostridium spp.

Some Clostridium organisms have the potential to become industrial platforms. However, high-throughput approaches to engineering strains require an increase in the toolkit available for genetic manipulation, which is critical to understanding Clostridium strains to develop strategies to control or exploit them. Some strains have developed gene-editing systems, and the ability to precisely edit the genome gives an advantage in the development of therapeutic strains. By deleting specific genes or modifying their expression, the host's phenotype can be adjusted to suit a given application. Most of the gene editing methods that have been reported based on Clostridium species are based on gene editing systems.

Micrographs of C.novyi spores and outgrowth.Fig.1 Procedure for genetic manipulations in clostridia for heterologous protein secretion.1

The progress in synthetic biology tools of Clostridium has played a key role in the development of biological therapeutic drugs based on Clostridium. Genetic manipulation of Clostridium sporogenes or the probiotic Clostridium butyricum results in the production of bioactive interleukin-2 (IL-2), porcine epidermal growth factor (pEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and glucagon-like peptide-1 (GLP-1).

Advantages

  • Targeted delivery: Clostridium species can selectively target and colonize tumor tissues.
  • Prodrug activation: Clostridium strains can be engineered to express enzymes that activate prodrugs (inactive drugs).
  • Immunomodulation: Genetically modified Clostridium can produce immunomodulatory molecules.
  • Biosurgery: Selectively lyse tumor cells.
  • Oral Vaccination

Frequently Asked Questions

Can Clostridium be genetically modified into a therapeutic strain?

Yes, Clostridium spp. can be genetically modified into therapeutic strains. Researchers have successfully engineered Clostridium species for various therapeutic applications, including cancer treatment and vaccine development. These advancements highlight the potential of Clostridium spp. as a versatile platform for developing innovative therapeutic strategies.

Which Clostridium bacteria have been used as probiotic chassis?

Several Clostridium species have been explored as probiotic chassis due to their beneficial effects on gut health. Some examples include:
  1. Clostridium butyricum: Known for producing butyrate, which supports intestinal health and has anti-inflammatory properties.
  2. Clostridium sporogenes: Often used in combination with other probiotics to enhance gut microbiota balance.
  3. Clostridium beijerinckii: Studied for its potential to produce beneficial metabolites and improve gut health.

Can Creative Biolabs provide gene editing services for Clostridium?

Yes, Creative Biolabs offers gene editing services for Clostridium spp. They provide a range of services, including gene knock-out, gene knock-in/gene insertion, and the construction of engineered strains.

The Clostridium species have shown promise in maintaining intestinal homeostasis, alleviating inflammation, and supporting overall gut health. Creative Biolabs has accumulated a lot of expertise and project experience in Clostridium and gene editing, if you have a genetic modification project that involves engineered Clostridium spp., please feel free to contact us for more.

Resources

Reference

  1. 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. 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.

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