TopAct™
How Does it Work?
The human gastrointestinal (GI) system is a large and complex organ, integrating vital physiological processes such as food intake and the regulation of immunity, energy balance and metabolism.
Because of the large diversity of pharmacologically relevant receptors present in GI tissues, TopAct™ can address a broad variety of gastrointestinal, immunological and metabolic diseases.
The implementation of TopAct™ technology to create a novel ActoBiotic™ comprises the following steps:
Engineering of the therapeutic strain
In a first step, sophisticated genetic techniques are used to insert a gene, encoding the desired therapeutic protein (or peptide), into the chromosome of a Lactococcus lactis bacterium. The technology ensures that the bacterium is able to express the gene at sufficient levels, that the relevant protein is efficiently secreted, and that the protein folds in the appropriate three-dimensional structure for proper biological activity.
As part of the same engineering process, a gene essential for survival of the bacterium is deleted. The newly created organism now becomes entirely dependent on an external source of a particular nutrient (thymidine) to survive. This elegant containment system ensures that the therapeutic Lactococcus lactis strain cannot survive outside of the human body, and that it dies quickly if released into the environment.
Large-scale production
When such a newly engineered therapeutic strain of Lactococcus lactis has been created in the laboratory, the next step involves its production at large scale, by industrial fermentation.
Because Lactococcus lactis is a well-known species and its manufacturing at large scale has been optimized by the food industry, this is a very efficient, well-characterized and straightforward process.
Formulation into an ActoBiotic™
After fermentation, the bacteria are freeze-dried (lyophilized) and milled as a dry powder. This powder is then formulated into capsules or an oral rinsing solution for administration. A new ActoBiotic™ is ready!
Administration of the ActoBiotic™ by the patient
When a patient ingests an ActoBiotic™ capsule, it will pass through his stomach and subsequently dissolve in his intestinal tract, where it will release the therapeutic Lactococcus lactis bacteria. Once the bacteria are released into the intestinal tract, they become metabolically active and start secreting their therapeutic protein.
Because the therapeutic Lactococcus lactis bacteria are contained and non-colonizing, they will only remain in the patient’s intestines for a few hours. During this time, they will continuously secrete appropriate amounts of therapeutically active protein, ensuring an efficient interaction of the therapeutic protein with target receptors located in or around the intestinal tissues.