Senti has a proprietary synthetic biology platform for development of therapeutics. The company uses genetic circuits to program cell therapies so that they have localized action, sensors, dynamic responses and safety control. Senti has a design platform for synthetic gene circuits for fast design, building and testing of therapeutic circuits.
The company aims to make gene therapies more adaptive and able to respond dynamically to disease conditions. Senti’s technology platform aims to allow cellular therapies to be controlled after they are administered and respond in a multifactorial way depending on the disease state and desired outcome.
Senti is developing T cell immunotherapies that target cancer using chimeric antigen receptors (CARs). One of their therapies in development is called the "split universal, and programmable" (SUPRA) CAR-T system. The SUPRA CAR system allows T cells to switch targets without re-engineering them and T cell activation can be fine tuned as well as sense and logically respond to multiple antigens. These characteristics may help these CAR-T cells to respond to relapse, mitigate over-activation and make the therapy more specific.
Usually CARs are expressed as full-length fusion proteins composed of ligand-binding, transmembrane and signaling domains. SUPRA CAR systems have two components, a zipCAR and a zipFv fragment. The zipCAR has intracellular signaling domains connected by a transmembrane segment to an extracellular domain that has a protein structural motif called a leucine zipper. The zipFv has a ligand-binding scFv domain fused to a second leucine zipper. Engineered T-cells that express zipCARs are not functional until zipFv proteins are added that have matching leucine zippers. Functional CAR reconstitution can be inhibited by adding a competing zipFv that dimerizes with the first zipFv.
The system makes the cellular therapy capable of Boolean-logic signal integration such as OR-gate and A-and-not-B signal by adding different zipFv sequences. Antigen specificity and binding affinity of the CAR is determined by externally added zipFv sequences. In principle the system could allow a generic or off-the-shelf zipCAR-T cell product, where the antigen specificity can be altered during the treatment course.
In their 2018 Cell publication about the SUPRA CAR system, authored by Cho, Collins and Wong, human transcription factors were used to derive leucine zipper domains for SUPRA CAR-T cell control of tumor growth in mouse models.
Co-founder and CEO Dr. Tim Lu, (M.D.,Ph.D.) is an Associate Professor at MIT in Biological Engineering, Electrical Engineering and Computer Science and co-founder of Synlogic, Tango Therapeutics, Sample6, Eligo BiomX and Engine Biosciences. In Fall 2018, Gary Lee, Ph.D., previously with Sangamo Therapeutics, joined Senti as Chief Scientific Officer. Senti’s Chief Financial Officer Curt Herberts also comes from Sangamo.
On February 27, 2018 Senti Biosciences completed their series A funding round with $53 million in funding from New Enterprise Associates (lead investor), 8VC, Amgen Ventures, Pear Ventures, Lux Capital, Menlo Ventures, Allen & Company, Nest.Bio, Omega Funds, Goodman Capital, and LifeForce Capital.
Gary Lee, Ph.D.
Chief Scientific Officer
Philip Lee, Ph.D.
Curt Herberts, M.B.S.
Chief Financial Officer and Chief Business Officer
Jim Collins, Ph.D.
Tim Lu, M.D., Ph.D.
Wilson Wong, Ph.D.
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- ImmunotherapyImmunotherapy aims to treat disease through activation or suppression of an immune response. For example activating immunotherapies can target cancer and suppressive immunotherapies can target autoimmunity.
- Chimeric antigen receptorA lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.
- BiotechnologyBiotechnology can refer to the application of science and technology to living organisms or the use of living organisms, their parts, products or models thereof to solve a problem, produce knowledge or produce goods and services. Biotechnology may involve the alteration of living or non-living materials.
- Synthetic biologyInterdisciplinary branch of biology and engineering, applying multiple disciplines to build artificial biological systems for research, engineering, and medical applications.