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Empowering gene delivery with protein engineering platforms

Gene Therapy volume 30, pages 775–782 (2023)Cite this article

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Abstract

The repertoire of therapeutic proteins has been substantially augmented by molecular engineering approaches, which have seen remarkable advancement in recent years. In particular, advances in directed evolution technologies have empowered the development of custom-designed proteins with novel and disease-relevant functions. Whereas engineered proteins have typically been administered through systemic injection of the purified molecule, exciting progress in gene delivery affords the opportunity to elicit sustained production of the engineered proteins by targeted cells in the host organism. Combining developments at the leading edge of protein engineering and gene delivery has catapulted a new wave of molecular and cellular therapy approaches, which harbor great promise for personalized and precision medicine. This mini-review outlines currently used display platforms for protein evolution and describes recent examples of how the resulting engineered proteins have been incorporated into DNA- and cell-based therapeutic platforms, both in vitro and in vivo. Collectively, the strategies detailed herein provide a framework for synthesizing molecular engineering workflows with gene therapy systems for a breadth of applications in research and medicine.

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Fig. 1: Schematic representations of protein display systems.
Fig. 2: Gene delivery of engineered proteins.
Fig. 3: Advances in Chimeric Antigen Receptor (CAR) engineering.

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Data sharing is not applicable to this paper as no datasets were generated or analyzed during the current study.

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Acknowledgements

Figures 1, 2, and 3 were created with BioRender.com and are used with permission of the copyright holder, Biorender.

Funding

The authors acknowledge funding from National Institutes of Health (R01EY031097) and an Allegheny Health Network-Johns Hopkins Cancer Research Fund award. M.K. and K.P. are recipients of National Science Foundation Graduate Research Fellowship Program awards.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Monika Kizerwetter, Kevin Pietz & Jamie B. Spangler

  2. Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD, USA

    Monika Kizerwetter, Kevin Pietz, Luke M. Tomasovic & Jamie B. Spangler

  3. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

    Luke M. Tomasovic & Jamie B. Spangler

  4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  5. Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  6. Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  7. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  8. Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Jamie B. Spangler

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M.K., K.P., L.M.T., and J.B.S. wrote and revised the paper.

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Kizerwetter, M., Pietz, K., Tomasovic, L.M. et al. Empowering gene delivery with protein engineering platforms. Gene Ther 30, 775–782 (2023). https://doi.org/10.1038/s41434-022-00379-6

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