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Biomaterials, Available online 10 April 2021, 120798 | https://doi.org/10.1016/j.biomaterials.2021.120798 A Novel Therapeutic Modality using CRISPR-Engineered Dendritic Cells to Treat Allergies

Byoungjae Kim^a,b,1, Young Eun Lee^c,d,1, Ji Woo Yeon^a, Ga-Yeon Go^c, Junhyoung Byun^a, Kijeong Lee^a, Hyomin K. Lee^e, Junho K. Hur^f,g, Mihue Jang^c,h,*, Tae Hoon Kim^a,*

^aDepartment of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, 02841, Republic of Korea
^bNeuroscience Research Institute, Korea University, College of Medicine, Seoul, 02841, Republic of Korea
^cCenter for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea
^dDepartment of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea
^eDepartment of Medicine, Major in Medical Genetics, Graduate School, Hanyang University, Seoul, 04763, Republic of Korea
^fDepartment of Genetics, College of Medicine, Hanyang University, Seoul, 04763, Republic of Korea
^gGraduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea
^hKHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea

1These authors contributed equally to this work.

*Corresponding author

Abstract

Despite the important roles of dendritic cells (DCs) in airway allergies, current therapeutic strategies such as drugs, allergen immunotherapy and biologics haven’t been targeted at them. In this study, we established a promising DC-based therapeutic approach for the alleviation of allergic rhinitis (AR)-associated allergic reactions, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated targeted gene disruption. RNA sequencing analysis revealed upregulation of vacuolar protein sorting 37B (VPS37B) in AR-derived DCs, indicating a novel molecular target. Following antigen presentation, VPS37A and VPS37B enabled endocytosis of the mannose receptor, which recognizes the house dust mite (HDM) allergen Der p 1. DCs with targeted disruption of VPS37A/B alleviated Th2 cytokine production when co-cultured in vitro with allogeneic naïve CD4+ T cell from patients with AR. Furthermore, nasal administration of Vps37a/b-disrupted bone marrow DCs to a mouse model of AR resulted in strongly reduced AR-related symptoms. Thus, this novel modality using genetically engineered DCs can provide an effective therapeutic and preventative strategy for allergic diseases.

Keywords : dendritic cells, CRISPR, vacuolar protein sorting 37, adoptive cell therapies, allergies

논문정보

형식Research article
게재일2021년 04월 (BRIC 등록일 2021-04-19)
연구진국내 연구진
분야 의약학 > 응용의학

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