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Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency

Lacey A Perdue, Priscilla Do, Camille David, Andrew Chyong, Anna Kellner, Amanda Ruggieri, Hye Ryong Kim, Khalid Salaita, Gregory B Lesinski, Christopher C Porter, View ORCID ProfileErik C Dreaden
doi: https://doi.org/10.1101/2020.02.13.948240
Lacey A Perdue
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
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Priscilla Do
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
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Camille David
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
4Department of Pediatrics, Emory School of Medicine
5Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory School of Medicine
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Andrew Chyong
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
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Anna Kellner
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
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Amanda Ruggieri
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
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Hye Ryong Kim
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
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Khalid Salaita
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
2Department of Chemistry, Emory University
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
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Gregory B Lesinski
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
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Christopher C Porter
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
4Department of Pediatrics, Emory School of Medicine
5Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory School of Medicine
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Erik C Dreaden
1Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
3Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University
4Department of Pediatrics, Emory School of Medicine
5Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory School of Medicine
6Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology
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  • ORCID record for Erik C Dreaden
  • For correspondence: edreaden@gmail.com
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ABSTRACT

Cytokine signaling is challenging to study and therapeutically exploit as the effects of these protein are often pleiotropic. A subset of cytokines can, however, exert signal specificity via association with latency-inducing proteins which cage the cytokine until disrupted by discreet biological stimuli. Inspired by this precision, here we describe a strategy for synthetic induction of cytokine latency via modification with photo-labile polymers that mimic latency while attached, then restore protein activity in response to light, thus controlling the magnitude, duration, and location of cytokine signals. We characterize the high dynamic range of latent cytokine activity modulation and find that polymer-induced latency, alone, can prolong in vivo circulation and bias receptor subunit binding. We further show that protein de-repression can be achieved with near single-cell resolution and demonstrate the feasibility of transcutaneous photoactivation. Future extensions of this approach could enable multicolor, optical reprogramming of cytokine signaling networks and more precise immunotherapies.

Footnotes

  • ↵* e.dreaden{at}emory.edu, e.dreaden{at}gatech.edu

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Posted February 14, 2020.
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Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency
Lacey A Perdue, Priscilla Do, Camille David, Andrew Chyong, Anna Kellner, Amanda Ruggieri, Hye Ryong Kim, Khalid Salaita, Gregory B Lesinski, Christopher C Porter, Erik C Dreaden
bioRxiv 2020.02.13.948240; doi: https://doi.org/10.1101/2020.02.13.948240
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Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency
Lacey A Perdue, Priscilla Do, Camille David, Andrew Chyong, Anna Kellner, Amanda Ruggieri, Hye Ryong Kim, Khalid Salaita, Gregory B Lesinski, Christopher C Porter, Erik C Dreaden
bioRxiv 2020.02.13.948240; doi: https://doi.org/10.1101/2020.02.13.948240

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