A New Treatment Modality
For adaptive, programmable therapeutics to be effective over extended periods, cells and objects placed in the body must avoid fibrosis caused by the foreign body response of the immune system. The Afibromer™ biomaterials of the Sigilon platform avoid the fibrotic response, allowing engineered cells implanted in the body to deliver therapeutic molecules for extended periods of time.
These engineered cells can either deliver molecules at a constant rate or be programmed using the techniques of synthetic biology to respond to changing conditions, such as intermittent flare-ups of disease symptoms (e.g., flare-ups that are characteristic of certain autoimmune diseases) or fluctuating blood levels of specific factors like glucose (e.g., conditions relevant to the treatment of diabetes).
Synthetic biology tools and programmable genetic circuits create new possibilities for the treatment of complex diseases. Sigilon therapeutics can be programmed to sense changing conditions and respond appropriately, acting as “smart” medicines inside the body. This is unlike gene therapies or RNA interference, which cannot be adjusted once they are introduced into the body.
We have developed proprietary engineered cells that are combined with Afibromer™ biomaterials to create effective therapeutics. These cells:
- express high levels of desired protein
- survive well in an encapsulation environment
- undergo measured division
- can be produced in large scale
- are of a similar type to cells previously used in clinical applications
- provide the ability to easily insert and remove different gene expression cassettes for different applications
In preclinical models, we have demonstrated that novel Afibromer™ polymer chemistry conjugated to a modified alginate can prevent the foreign body response against allogeneic cells for at least 12 months. In clinical applications, we envision therapeutics that function for multiple years following a single intervention.
Engineered cells (in green) encapsulated in approximately 1 mm-diameter Afibromer™ beads
Afibrotek™ Chemistry Library
We have a proprietary library of compounds that can be used to modify any biomaterial to prevent the foreign body response often seen when medical devices are placed into a patient. We have demonstrated the effectiveness of these compounds on a range of biomaterials which are used in many medical devices.
For example, when implanted for the same period of time in an animal model, stainless steel beads coated with Afibrotek™ chemistry (left panel) do not result in the fibrosis that is observed with uncoated stainless steel materials of similar size and shape (right panel).
In the figure above, a marker of macrophage immune cells (CD68 in green) and a marker of activated fibrogenic cells (SMA in red) helps visualize the difference in immune detection between steel beads coated with Afibrotek™ chemistry (left panel) and uncoated stainless steel spheres (right panel). Similar differences are observed with other materials that may be used in medical implants or devices, such as glass or plastics.