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Engineering Closed-Loop, Autoregulatory Gene Circuits for Osteoarthritis Cell-Based Therapies

  • Osteoarthritis (M Goldring and T Griffin, Section Editors)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Genetic engineering offers the possibility to simultaneously target multiple cellular pathways in the joints affected by osteoarthritis (OA). The purpose of this review is to summarize the ongoing efforts to develop disease-modifying osteoarthritis drugs (DMOADs) using genetic engineering, including targeting approaches, genome editing techniques, and delivery methods.

Recent Findings

Several gene circuits have been developed that reprogram cells to autonomously target inflammation, and their efficacy has been demonstrated in chondrocytes and stem cells. Gene circuits developed for metabolic disorders, such as those targeting insulin resistance and obesity, also have the potential to mitigate the impact of these conditions on OA onset and/or progression.

Summary

Despite the strides made in characterizing the inflammatory environment of the OA joint, our incomplete understanding of how the multiple regulators interact to control signal transduction, gene transcription, and translation to protein limits the development of targeted disease-modifying therapeutics. Continuous advances in targeted genome editing, combined with online toolkits that simplify the design and production of gene circuits, have the potential to accelerate the discovery and clinical application of multi-target gene circuits with disease-modifying properties for the treatment of OA.

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Funding

The preparation of this manuscript was supported by the OREF Soft Tissue Repair and Regeneration Sports Medicine Grant in Honor of Russell F. Warren, MD in collaboration with the American Orthopaedic Society for Sports Medicine (AOSSM) #18-051.

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  1. Department of Biomedical Engineering, University of Michigan, Lurie Biomedical Engineering Building, RM 2170, 1101 Beal Ave, Ann Arbor, MI, 48105, USA

    Rhima M. Coleman

  2. Department of Mechanical Engineering, University of Michigan, MI, Ann Arbor, USA

    Rhima M. Coleman

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Coleman, R.M. Engineering Closed-Loop, Autoregulatory Gene Circuits for Osteoarthritis Cell-Based Therapies. Curr Rheumatol Rep 24, 96–110 (2022). https://doi.org/10.1007/s11926-022-01061-x

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