The Synchronized Lysis Circuit

Gencirq’s Synchronized Lysis Circuit may be conceptualized as a therapeutic delivery system which self-triggers within a tumor. The circuit uses bacterial lysis, which bursts open bacteria, as a mechanism to release a genetically-encoded payload.

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How it works

After bacteria colonize a tumor, the SLC is selectively activated when the bacterial population reaches a threshold density. Activation leads to synchronized lysis, which controls the release of genetically-encoded therapeutics and immunostimulatory ligands in a cyclical manner. The lysis also acts to maintain low levels of bacteria for enhanced safety.

Publications

Learn more about GenCirq’s technology from the following publications and news articles:

Genetic circuits:

  • Din, M.O.*, Danino, T.*, Prindle, A., Skalak, M., Selimkhanov, J., Allen, K., Julio, E., Atolia, E., Tsimring, L.S., Bhatia, S.N. and Hasty, J., 2016. Synchronized cycles of bacterial lysis for in vivo delivery. Nature. (Link)
    • Highlighted in scientific reviews:
      • Zhou, S., Gravekamp, C., Bermudes, D. and Liu, K., 2018. Tumour-targeting bacteria engineered to fight cancerNature Reviews Cancer. (Link)
      • Wu, M.R., Jusiak, B. and Lu, T.K., 2019. Engineering advanced cancer therapies with synthetic biologyNature Reviews Cancer. (Link)
  • Danino, T.*, Prindle, A.*, Kwong, G.A., Skalak, M., Li, H., Allen, K., Hasty, J. and Bhatia, S.N., 2015. Programmable probiotics for detection of cancer in urine. Science translational medicine. (Link)

Therapeutic delivery:

  • Gurbatri, C., Iona, L., Vincent, R., Coker, C., Castro, S., Treuting, P., Hinchliffe, T., Arpaia, N., Danino, T., 2020. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies. Science translational medicine. (Link)
  • Chowdhury, S., Castro, S., Coker, C., Hinchliffe, T.E., Arpaia, N. and Danino, T., 2019. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nature medicine. (Link)