Gene Circuit Technology Platform
Key Challenges to Existing Disease Treatments and Our Gene Circuit Solutions
Diseases often involve complex biological interactions, which limit the effectiveness of existing therapeutics that only have single mechanisms of action and are unable to adapt to dynamic disease states. We characterize these key challenges in the following four categories:
Target Heterogeneity
Target Heterogeneity: Many diseases are heterogeneous and express antigens that are also present on healthy cells. For example, most cancers do not have a single antigen target that is uniformly expressed on all cancer cells with limited to no expression on non-cancerous cells. The ability to precisely distinguish between diseased cells and healthy cells has been a central challenge to date with monoclonal antibodies, antibody-drug conjugates and single-target CAR therapies. Modalities that can respond to multiple biomarkers, rather than just a single one, have the potential to open up the opportunity for more precise and efficacious medicines.
Disease Evasion
Disease Evasion: Disease pathologies are multifaceted. For example, diseases can evade the immune system or acquire resistance to single-target treatments by activating other biological pathways. The tumor microenvironment of many solid tumors suppresses cancer-fighting immune cells via multiple pathways. Overcoming these complex barriers– by using multiple individual drugs together can be difficult. A gene or cell therapy with the ability to activate multiple anti-tumor pathways within a single product could help limit disease evasion and may improve the durability of responses to treatment.
Narrow Therapeutic Window:
Once administered to a patient, conventional medicines, including cell and gene therapies, cannot be tuned up or down, which makes it difficult to find the optimal dose, especially for diseases that have a narrow therapeutic window. The ability to create therapeutics that can be titrated or regulated in vivo in the patient may lead to enhanced efficacy and safety.
Dynamic Disease Conditions
Disease conditions are dynamic and vary in space and time. For example, diseases may manifest only in certain tissues, or have a waxing and waning progression over time. Conventional therapies are (i) static, (ii) have a predefined activity around a single mechanism of action that cannot be modified post-administration and (iii) do not adapt to these dynamic conditions, thus limiting their efficacy, specificity and safety. Developing dynamic therapeutics that are able to sense, and respond to, dynamic conditions may address this challenge.
Gene Circuit Solutions
We believe that our core gene circuit platform technologies may enable us to engineer smarter medicines to address fundamental disease challenges in the clinic using our four gene circuit platform technologies.
Logic Gating
Multi-Arming
Regulator Dial
Smart Sensors
Gene Circuit Technology Platform: Broad Applicability Across Treatment Modalities and Disease Areas
Design. Build. Test. Learn.
Senti Bio has established, and continues to scale, a powerful Design-Build-Test-Learn development engine to generate our therapeutic gene circuits. Unique to Senti Bio’s approach is the speed, quantity and quality of the multiple types of gene circuits designed, resulting in thousands of gene circuits engineered to date. Senti Bio believes that this approach to programming gene circuits is broadly applicable toward engineering optimal efficacy, precision and control into many cell or gene based medicines.
