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A Synthetic Gene Circuit for Self-Regulating Delivery of Biologic Drugs in Engineered Tissues
Lara Pferdehirt1,2,3,4, Alison K Ross1,2,3,4, Jonathan M Brunger5
11 Department of Orthopedic Surgery, Washington University in Saint Louis, Saint Louis, Missouri.
Impact Statement:
We engineered a synthetic transcription system based on nuclear factor kappa-light-chain-enhancer of activated B cells signaling that can attenuate the effects of the inflammatory cytokine interleukin (IL)-1α in a self-regulating manner. This system responds in a time- and dose-dependent manner to rapidly produce therapeutic levels of IL-1 receptor antagonist (IL-1Ra). The use of lentiviral gene therapy allows this system to be utilized through different transduction methods and in different cell types for a variety of applications. Broadly, this approach may be applicable in developing autoregulated biologic systems for tissue engineering and drug delivery in a range of disease applications.
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