Scientific Presentations & Publications

Senti Bio's team is pioneering the use of gene circuits for potentially broad therapeutic application. The publications highlighted below represent a sample of the team's innovative and foundational work.

Authors: Brian Garrison , Han Deng, Gozde Yucel, Nicholas Frankel, Russell Gordley, Michelle Hung, Derrick Lee, Marcus Gainer, Nelia Leemans, Alice Lam, Wilson Wong, Philip Lee, Tim Lu, Gary Lee

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Authors: Marcela Guzman Ayala, Michelle Hung, Poornima Ramkumar, Deepika Kaveri, Elizabeth Leiner, Priscilla Wong, Ronni Ponek, Brett Kiedaisch, Wesley Gorman, Russell Gordley, Rebecca Cottman, Kelly Lee, Allison Drain, Ahmad S Khalil, Gary Lee

 

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Authors: Michelle Hung, Assen Roguev, Yin Yin Chong, Carmina Blanco, Travis Wood, Brandon Lee, Brett Kiedaisch, Russell Gordley, Gary Lee, Tim Lu

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Authors: Travis Wood, Abla Bakir, Carmina Blanco, Dharini Iyer, Wesley Gorman, Haritha Lakshmireddy, Charity Vilchez Juang, Denny Nguyen, Martin Giedlin, Philip Lee

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Authors: Alba Gonzalez, Michelle Hung, Marcela Guzman, Aldo Sotelo, Nicholas Frankel, Yin-Yin Chong, Deepika Kaveri, Poornima Ramkumar, Elizabeth Leiner, Priscilla Wong, Ronni Ponek, Kelly Lee, Alyssa Mullenix, Russell Gordley, Gary Lee

 

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Authors: Brian S. Garrison, PhD , Han Deng, PhD, Gozde Yucel , PhD, Nicholas W. Frankel, PhD, Marcela Guzman Ayala, PhD, Russell Gordley, PhD, Michelle Hung, PhD, Derrick Leem, Marcus Gainer, Kathryn Loving, PhD, Jenny Chien, Tiffany Pan, MS, Wesley Gorman, Nelia Leemans , MS, Alice Lam, Poornima Ramkumar, PhD, Travis Wood, Wilson Wong, PhD, Philip Lee, PhD, Tim Lu, MD PhD, Gary Lee, PhD

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Authors: Alba Gonzalez, Assen Roguev, Brian Garrison, Nicholas Frankel, Derrick Lee, Marcus Gainer, Alyssa Mullenix, Russel Gordley, Kathryn Loving, Jenny Chien, Gary Lee

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Authors: Dharini Iyer, Wesley Gorman, Carmina Blanco, Travis Wood, Mario Lorente, Charity Vilchez Juang, Denny Nguyen, Brandon Lee, Brett Kiedaisch, Philip Lee

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Authors: Travis Wood, Abla Bakir, Carmina Blanco, Dharini Iyer, Brett Kiedaisch, Wesley Gorman, Mario Lorente, Brandon Lee, Denny Nguyen, Philip Lee

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Authors: Michelle Hung, Divya Israni, Huishan Li, Yin Yin Chong, Poornima Ramkumar , Allison Drain, Allison Quach, Mengxi Tian, Rishi Savur, Niran Almudhfar, Chen Ting Lee, Abla Bakir, Edwin Cruz, Carmina Blanco, Travis Wood, Mario Lorente, Brandon Lee, Brett Kiedaisch, Russell M. Gordley, Marcela Guzman Ayala, Ahmad Khalil, Gary Lee, Tim Lu

 

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Authors: Brian S. Garrison, Han Deng, Gozde Yucel , Nicholas W. Frankel, Marcela Ayala Guzman, Russell M. Gordley , Michelle Hung, Derrick Lee, Marcus Gainer, Kathryn Loving, Jenny Chien , Tiffany Pan, Wesley Gorman, Nelia Leemans , Alice Lam, Travis Wood, Wilson Wong, Philip Lee, Tim Lu, Gary Lee

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Nicholas W. Frankel, Seunghee Lee, Derrick Lee, Marcus Gainer, Brian S. Garrison, Travis Wood,Wesley Gorman, Russell Gordley, Marcela Guzman Ayala, Tim Lu, Gary Lee, Wison Wong

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Authors: Alba Gonzalez-Junca, Assen Roguev, Brian Garrison, Nicholas Frankel, Derrick Lee, Marcus Gainer, Alyssa Mullenix, Russell Gordley, Kathryn Loving, Jenny Chien, Gary Lee

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Cho JH, Collins JJ, Wong WW. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Cell 173:1426 (2018). doi: 10.1016/j.cell.2018.03.038.

Wilson Wong and co-authors introduce a unique split/universal chimeric antigen receptor (CAR) targeting system called SUPRA that affords tunable control over immune cell activity via soluble antigen-binding molecules. SUPRA CAR can fine-tune immune cell activation strength to mitigate toxicity, SUPRA CAR can sense and logically respond to multiple antigens to prevent relapse and enhance safety, and SUPRA CAR can inducibly control cell-type-specific signaling.

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Scheller L, Strittmatter T, Fuchs D, Bojar D, Fussenegger M. Nature Chemical Biology 14:723 (2018).  doi: 10.1038/s41589-018-0046-z.

Here, Martin Fussenegger and coworkers describe a novel generalized extracellular molecule sensing (GEMS) protein architecture that, working in conjunction with synthetic promoters, can be adapted to detect a wide diversity of inputs including soluble signals. Examples of input signals detected here include the synthetic azo dye, nicotine, a peptide tag, and the PSA (prostate-specific antigen) biomarker.

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Nissim L, Wu MR, Pery E, Binder-Nissim A, Suzuki H, Stupp D, Wehrspaun C, Tabach Y, Sharp PA, Lu TK. Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Cell 171:1138 (2017). doi: 10.1016/j.cell.2017.09.049.

In this publication, Tim Lu and co-workers present a proof-of-concept immunomodulatory gene circuit platform that enables tumor-specific expression of immunostimulators. Tumor-specific expression was achieved using synthetic cancer-specific promoters and an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when two promoters are mutually active. In preclinical models, a lentiviral cancer gene therapy encoding this gene circuit triggered tumor-specific expression, recruitment of T cells, and immune-mediated elimination of tumors.

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Saxena P, Heng BC, Bai P, Folcher M, Zulewski H, Fussenegger M. A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells. Nature Communications 7: 11247 (2016). doi: 10.1038/ncomms11247.

While recent advances in regenerative medicine have permitted the generation of off-the-shelf tissue grafts suitable for a wide variety of medical applications, the low efficiency and high cost of cellular differentiation protocols represent significant hurdles. In this work, Martin Fussenegger and coworkers describe a gene circuit approach that relies on low-cost inputs (like vanillic acid, a relative of the primary extract component of vanilla bean) to efficiently control the derivation of functional pancreatic insulin-producing cells from precursor cells for the treatment of Type 1 diabetes. 

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Schukur L, Geering B, Charpin-El Hamri G, Fussenegger M. Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Science Translational Medicine 7:318 (2015). doi: 10.1126/scitranslmed.aac4964.

Psoriasis is a chronic inflammatory skin disease characterized by a relapsing-remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL-22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Here, Martin Fussenegger and colleagues designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL-22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL-4 and IL-10, which have been shown to be immunomodulatory in patients.

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