A New Platform for Fully Customizable Transcriptional Receptors.

We engineered a suite of compact Synthetic Intramembrane Proteolysis Receptors (SNIPRs) with tunable sensing and transcriptional response abilities in T cells. Our design framework can be applied to a range of therapeutic cells suitable for clinical translation.
A New Platform for Fully Customizable Transcriptional Receptors.

Synthetic biology has established powerful tools for precise and complex control of cellular function. Engineering such systems to meet clinical requirements remains challenging but has enormous implications for the successful treatment of human disease. Here, we adopted a clinically driven design process to build and test receptors for the autonomous control of therapeutic cells. We examined the function of the key domains of regulated-intramembrane-proteolysis (RIP) receptors and show that modular assembly and engineering of the component domains can generate a suite of compact and SyNthetic Intramembrane Proteolysis Receptors (SNIPRs) with tunable sensing and transcriptional response abilities in T cells. We demonstrate the potential transformative utility of this new receptor platform by engineering cells for multi-antigen recognition and delivery of dosed, bioactive payloads relevant to the treatment of disease. Our design framework enables the development of a fully customizable transcriptional receptors platform for the programming of therapeutic cells suitable for clinical translation.

Selected Publications

Design and modular assembly of synthetic intramembrane proteolysis receptors for custom gene regulation in therapeutic cells

Research Team

Axel Hyrenius-Wittsten, Ph.D.
Axel Hyrenius-Wittsten, Ph.D.

Postdoctoral Fellow

Josef Alavi
Josef Alavi

Staff Research Associate

Raymond Liu, Ph.D.
Raymond Liu, Ph.D.

Postdoctoral Fellow

Dan I. Piraner, Ph.D.
Dan I. Piraner, Ph.D.

Postdoctoral Fellow

Iowis Zhu
Iowis Zhu

MD/PhD Student

News

Media highlights of Kole and the lab’s research.
'Smart' immune cells kill tumours and stop them regrowing in mice
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Attacking glioblastoma and other solid tumors with CAR-Ts that target multiple antigens
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Tweaking Mother Nature, biologists aim for better cancer-fighting cells
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'Cell Bots' Chase Down Cancer, Deliver Drugs Directly to Tumors
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Synthetic Notch receptors were featured in Notable Advances 2016
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Kole Roybal receives the inaugural Sartorius & Science Magazine Prize in Regenerative Medicine and Cell Therapy 2018
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Boosting the immune system to fight cancer
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Cell Design Labs, Little Partner Of Kite Pharma, Pushes T-Cell Engineering Frontier
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