Gene Circuit Technology Platform

Gene Circuit Platform: Broad Applicability Across Treatment Modalities and Disease Areas

Senti Bio’s perspective on how gene circuit technologies can be utilized across modalities and corresponding therapeutic areas to address specific challenges facing existing medicines.

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.

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 have single mechanisms of action and are unable to adapt to dynamic disease states. We characterize these key challenges in four categories.

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Dynamic Conditions

Disease conditions are dynamic and vary in space and time. Current cell and gene therapies are not dynamic or highly specific, thus limiting the indications that they can address. Developing dynamic therapeutics that are able to sense, and respond to, these varying conditions would address this challenge.

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Lack of Specificity

Many diseases are heterogeneous and express antigens that are also present on healthy cells. The overlap of antigen expression on diseased and healthy cells limits the ability of existing therapies to target diseased cells at therapeutically relevant doses due to undesirable effects against healthy cells. The ability to distinguish between tumor cells and healthy cells would open up the opportunity for more precise and efficacious medicines.

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Narrow Dose 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 the patient may lead to enhanced efficacy and safety.

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Disease Evasion

Disease pathologies are multifaceted. Diseases can evade the immune system or acquire resistance to single-target treatments by activating other biological pathways. A gene or cell therapy with the ability to activate multiple anti-tumor pathways within a single product would help limit disease evasion and may improve durable responses to treatment.

Gene Circuit Solutions

Senti Bio categorizes its gene circuits into four gene circuit platform technologies.

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Smart Sensors: 

A gene circuit, or combination of gene circuits, designed to precisely detect cell type or disease environments, and distinguish between the “disease state” and “healthy state.” Conventional medicines are generally unable to dynamically change their behavior in response to cell or disease specific conditions.

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Logic Gating:

Gene circuits that are designed to enable cell and gene therapies to control their therapeutic activity in response to the presence or absence of multiple disease biomarkers.

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Regulator Dial:

Gene circuits that are designed to enable the precise tuning of therapeutic activity from a cell or gene therapy product.

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Multi-Arming:

Gene circuits that are designed to incorporate multiple payloads into a single cell or gene therapy product.