Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs.

Published

Journal Article

Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases.

Full Text

Duke Authors

Cited Authors

  • Brunger, JM; Zutshi, A; Willard, VP; Gersbach, CA; Guilak, F

Published Date

  • May 2017

Published In

Volume / Issue

  • 8 / 5

Start / End Page

  • 1202 - 1213

PubMed ID

  • 28457885

Pubmed Central ID

  • 28457885

Electronic International Standard Serial Number (EISSN)

  • 2213-6711

International Standard Serial Number (ISSN)

  • 2213-6711

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2017.03.022

Language

  • eng