A New Treatment Modality
For many years, researchers have worked towards implanted cell-based treatments to replace therapies for several chronic diseases. In the case of diabetes, one area of focus has been the development of implanted donor cells that can sense blood glucose and respond by secreting insulin. However, this approach suffers from a critical limitation: a patient’s immune system will recognize donor cells as foreign and then destroy them, unless the treatment is co-administered with immunosuppressant drugs. Use of the latter on a long-term basis is associated with significant risks including infection and cancer. This challenge partly explains why cell-based therapeutic implants are not yet more widespread. It also underscores the tremendous potential of Sigilon’s key innovation: The Shielded Living Therapeutics™ platform, which harnesses the power of therapeutic human cells without inducing an immune response.
Our engineered human cells can either deliver proteins at a constant rate or be programmed to respond to changing conditions using the techniques of synthetic biology, such as intermittent flare-ups of disease symptoms (e.g., flare-ups that are characteristic of certain autoimmune diseases) or fluctuating levels of circulating factors such as 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 and serious chronic diseases. Shielded Living 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.
Sigilon has developed proprietary engineered human cells that are combined with Afibromer technology to create effective therapeutics. These human cells:
- Express high levels of desired protein(s)
- Survive well in an encapsulation environment
- Can be produced at large scale
- Provide the ability to easily insert and remove gene expression cassettes for different applications
In experimental animal models, Shielded Living Therapeutics using Afibromer technology have resisted fibrosis for 12 months or more. Assuming this success can be repeated in humans, Sigilon’s hope is that Shielded Living Therapeutics could generate and secrete the natural biomolecules a patient needs over long periods of time, even years, maintaining constant therapeutic protein replacement. This goes beyond convenience and adherence and is expected to produce superior longer-term patient outcomes.
Engineered cells (in green) encapsulated in approximately 1 mm-diameter Afibromer™ beads
In addition to Afibromer, Sigilon has a proprietary library of other compounds that can be used to modify any biomaterial to prevent the foreign body response. Our Afibrotek library consists of numerous compounds with demonstrated effectiveness at preventing fibrosis on a range of biomaterials used in medical implants and devices.