A Novel Therapeutic Modality using CRISPR-Engineered Dendritic Cells to Treat Allergies
- A Novel Therapeutic Modality using CRISPR-Engineered Dendritic Cells to Treat Allergies
- 장미희; 고가연; 이영은; 김병재; 연지우; 변준형; 이기정; 이효민; 허준호; 김태훈
- CRISPR; Allergic treatment; Dendritic cell; Adoptive cell transfer
- Issue Date
- VOL 273, 120798
- 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 37 B (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 na？ve 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.
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