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

Tissue Eng Part A. 2019 May;25(9-10):809-820. doi: 10.1089/ten.TEA.2019.0027.

Abstract

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.

Keywords: arthritis; gene therapy; regenerative medicine; stem cells; synthetic biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Products / metabolism*
  • Gene Regulatory Networks*
  • Genes, Synthetic*
  • Genetic Therapy*
  • HEK293 Cells
  • Humans
  • Interleukin 1 Receptor Antagonist Protein* / biosynthesis
  • Interleukin 1 Receptor Antagonist Protein* / genetics
  • Interleukin-1alpha* / biosynthesis
  • Interleukin-1alpha* / genetics
  • Mice
  • Tissue Engineering*

Substances

  • Biological Products
  • IL1A protein, human
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1alpha