Kim, Byoungjae Lee, Young Eun Yeon, Ji Woo Go, Ga-Yeon Byun, Junhyoung Lee, Kijeong Lee, Hyomin K. Hur, Junho K. Jang, Mihue Kim, Tae Hoon 2024-01-19T14:32:40Z 2024-01-19T14:32:40Z 2021-09-05 2021-06 0142-9612 https://pubs.kist.re.kr/handle/201004/116930 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 ARderived 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 naive 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. English Pergamon Press Ltd. A novel therapeutic modality using CRISPR-engineered dendritic cells to treat allergies Article 10.1016/j.biomaterials.2021.120798 1 Biomaterials, v.273 Biomaterials 273 N scie scopus 000649667700002 2-s2.0-85104761282 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article DC-SIGN RECEPTOR ESCRT DIFFERENTIATION IMMUNOTHERAPY POLARIZATION RECOGNITION ACTIVATION ADHESION GUIDES Dendritic cells CRISPR Vacuolar protein sorting 37 Adoptive cell therapies Allergies