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Synthetic DNA Delivery of an Engineered Arginase Enzyme Can Modulate Specific Immunity In Vivo
Journal article   Open access   Peer reviewed

Synthetic DNA Delivery of an Engineered Arginase Enzyme Can Modulate Specific Immunity In Vivo

Makan Khoshnejad, Alfredo Perales-Puchalt, Yaya Dia, Peng Xiao, Ami Patel, Ziyang Xu, Xizhou Zhu, Kun Yun, Ishana Baboo, Rehman Qureshi, …
Molecular therapy. Methods & clinical development, v 18, pp 652-663
11 Sep 2020
DOI: https://doi.org/10.1016/j.omtm.2020.05.025
PMID: 32802913
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.omtm.2020.05.025View
Published, Version of Record (VoR) Open

Abstract

Arginase DNA Delivery Electroporation Immunosuppression Inflammation
Arginase is a complex and unique enzyme that plays diverse roles in health and disease. By metabolizing arginine, it can shape the outcome of innate and adaptive immune responses. The immunomodulatory capabilities of arginase could potentially be applied for local immunosuppression or induction of immune tolerance. With the use of an enhanced DNA delivery approach, we designed and studied a DNA-encoded secretable arginase enzyme as a tool for immune modulation and evaluated its immunomodulatory function in vivo. Strong immunosuppression of cluster of differentiation 4 (CD4) and CD8 T cells, as well as macrophages and dendritic cells, was observed in vitro in the presence of an arginase-rich supernatant. To further evaluate the efficacy of DNA-encoded arginase on in vivo immunosuppression against an antigen, a cancer antigen vaccine model was used in the presence or absence of DNA-encoded arginase. Significant in vivo immunosuppression was observed in the presence of DNA-encoded arginase. The efficacy of this DNA-encoded arginase delivery was examined in a local, imiquimod-induced, psoriasis-like, skin-inflammation model. Pretreatment of animals with the synthetic DNA-encoded arginase led to significant decreases in skin acanthosis, proinflammatory cytokines, and costimulatory molecules in extracted macrophages and dendritic cells. These results draw attention to the potential of direct in vivo-delivered arginase to function as an immunomodulatory agent for treatment of local inflammation or autoimmune diseases. [Display omitted] Arginase is a unique enzyme that plays a critical role in regulating the outcome of innate and adaptive immune responses. The immunomodulatory capabilities of arginase enzyme could potentially be applied for local inflammation or autoimmune diseases. Here, we report on a DNA-encoded secretable arginase enzyme as a tool for therapeutic immunomodulation.

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Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Medicine, Research & Experimental
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