Senti Bio Highlights Initial Gene Circuit Data From Collaborations at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting - Seite 2

Designing cell-state-specific synthetic promoters as Smart Sensors to control macrophage polarization
In collaboration with BlueRock Therapeutics

• Senti Bio discovered and validated M1-state-specific macrophage promoters that can be rationally re-engineered to improve promoter strength and M1 state-specific activity.
• State-specific synthetic promoter libraries were bioinformatically designed for high-throughput Massively Parallel Reporter Assay (MPRA) screening. The data shows that hits from these promoter libraries can be stronger and more selective than native promoters.
• The data demonstrated that state-specific promoters can be built into Smart Sensor circuits to control macrophage polarization logic.
  

BlueRock Therapeutics’ Poster Presentation
Engineering a gene circuit-enabled cell therapy with a Tamoxifen regulated safety switch for inducible cell death in human pluripotent stem cells (hPSCs) and their derivatives
BlueRock Therapeutics poster utilizing Senti Bio’s Gene Circuit technology

• One potential safeguard against risks associated with hPSCs is the implementation of a safety switch that can ablate transplanted cells from a patient.
• Senti Bio’s Safety Switch gene circuit has been successfully engineered into BlueRock's hPSCs for robust, stable, and ubiquitous expression of biological cargo.
• BlueRock has demonstrated that hPSCs harboring a novel TamCasp9-engineered Safety Switch gene circuit, expressed robustly from the GAPDH locus, enables transplanted cells to be removed with pharmacologically relevant concentrations of tamoxifen metabolites.
  

About Senti Bio

Our mission is to create a new generation of smarter medicines that outmaneuver complex diseases using novel and unprecedented approaches. To accomplish this, we are building a synthetic biology platform that may enable us to program next-generation cell and gene therapies with what we refer to as Gene Circuits. These novel and proprietary Gene Circuits are designed to reprogram cells with biological logic to sense inputs, compute decisions and respond to their cellular environments. We aim to design Gene Circuits to improve the intelligence of cell and gene therapies in order to enhance their therapeutic effectiveness, precision, and durability against a broad range of diseases that conventional medicines do not readily address.