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Mechanobiology

A Synthetic Gene Circuit for Self-Regulating Delivery of Biologic Drugs in Engineered Tissues

AUTHORS

Pferdehirt LLara , Ross AKAlison K , Brunger JMJonathan M , Guilak FFarshid . Tissue engineering. Part A. 2019 5 10; 25(9-10). 809-820

ABSTRACT

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.