Engineering Lactobacillus Services for Live Biotherapeutics Drug Discovery

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The development of Lactic acid bacteria (LAB) expression systems has stimulated studies aimed at determining the cellular localization of expressed antigens and the effect of localization on their immunogenic capacity. Additional studies and clinical trials will facilitate the use of recombinant LAB (RecLAB) as a novel therapeutic approach to the treatment of a wide variety of human diseases soon. Creative Biolabs specializes in providing custom live biotherapeutics product (LBP) services and products for researchers around the world, including Lactobacillus engineering strain construction services.

Background

Fig.1 Lactobacillus engineering. (Creative Biolabs Authorized)

The safety status, probiotic activities, and capacity to survive the passage through the gastrointestinal tract (GIT) make LAB excellent candidates for targeting therapeutic molecules. Most importantly, this approach reduces potential side effects associated with the classical systemic routes of drug delivery. Over the last 20 years, a large number of health benefits of RecLAB, particularly lactococcus and lactobacillus, have been demonstrated. Data obtained in the phase I clinical trial conducted with a recombinant strain of L. lactis secreting human IL-10 showed that the containment strategy used to construct the strain was not only safe and effective but also proved that mucosal delivery of IL-10 by a recLAB is feasible in humans. Lactobacillus species have already been used as a safe vaccine vector to deliver the different antigens and also served as a promising vaccine candidate against some experimentally induced diseases in birds. The administration of such vaccine constructs could propose many benefits: easy and noninvasive route of administration, high safety levels, cost-effectiveness, and capability of high induction of systemic and mucosal immunity against the foreign-expressed antigens.

Engineered Lactobacillus Chassis Strains at Creative Biolabs

Multiple Heterologous Proteins Can Be Expressed

Recombinant protein technologies have historically enabled the production of inexpensive therapeutic proteins at large scale, which have reached clinical settings.

  • Mucus binding proteins
  • Flagella, fimbriae and pili
  • Biofilm formation components
  • Synthetic Adhesins
  • Persistence enhancing factors
  • Prebiotics
  • Antimicrobial peptides (AMPs)

Examples of Applications

The expansion of synthetic biology tools to probiotic bacteria has enabled their genetic manipulation and triggered the development of living medicines. Engineered probiotic therapies should be able to produce a therapeutic molecule on demand and achieve GI tract colonization and integration into the resident microbial community.

  • Antibacterial or Antiviral Activity
  • Cancer Therapy
  • Metabolic Activity
  • Biosensing
  • Immune Modulation

Delivery Systems and Advantages of Mucosal Delivery Vehicles

  • LABs are non-pathogenic microorganisms and are considered safer than some attenuated vectors.
  • Engineered probiotics interact with the host mucosal immune system extensively and can be utilized to deliver enzymes, vaccines, antimicrobials, and cytokines.
  • The recombinant LAB strains can express multiple exogenous proteins, which may facilitate the development of multivalent vaccines.
  • LAB is not only used as live bacteria in mucosal immunity but also as effective as mucosal carriers.
  • Biotic sensors can be engineered into probiotics for use as non-invasive diagnostic tools.

Genome Editing in Lactobacillus

Gene editing is a revolutionary genetic engineering technique that can precisely modify specific target genes in an organism's genome. Effective gene editing of Lactobacillus to enhance strains with prebiotic properties, or introduce additional prebiotic functions as needed, will expand the use of Lactobacillus in food development, disease treatment, and nutritional health. With the development of more and more Lactobacillus genome sequencing work, it is imperative to study the function of a large number of unknown genes. The highly developed genetic engineering tools provide insight into a wide variety of organisms, especially those notorious for genetic manipulation or lack of effective genetic tools. Genome editing technology has made some progress in the application of Lactobacillus. Using gene editing technology to modify Lactobacillus may be a promising approach.

So far, several recombinant LABs have reached clinical trials. The first clinical study involved the use of Lactobacillus for human IL-10 secretion in patients with Crohn's disease. The treatment proved to be safe and well tolerated, with a reduction in Crohn's disease symptoms. Creative Biolabs is a USA biotech company, we are highly experienced in LBP development. Our team can provide you with the right support and expertise for each of the different stages of the development of your project. If you are interested in our recombinant Lactobacillus expression strain construction services, please contact us for more information.

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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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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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