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A novel therapeutic modality using CRISPR-engineered dendritic cells to treat allergies

Authors
Kim, ByoungjaeLee, Young EunYeon, Ji WooGo, Ga-YeonByun, JunhyoungLee, KijeongLee, Hyomin K.Hur, Junho K.Jang, MihueKim, Tae Hoon
Issue Date
6월-2021
Publisher
ELSEVIER SCI LTD
Keywords
Adoptive cell therapies; Allergies; CRISPR; Dendritic cells; Vacuolar protein sorting 37
Citation
BIOMATERIALS, v.273
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
273
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/137351
DOI
10.1016/j.biomaterials.2021.120798
ISSN
0142-9612
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 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.
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