A Novel Therapeutic Modality using CRISPR-Engineered Dendritic Cells to Treat Allergies

Title
A Novel Therapeutic Modality using CRISPR-Engineered Dendritic Cells to Treat Allergies
Authors
장미희고가연이영은김병재연지우변준형이기정이효민허준호김태훈
Keywords
CRISPR; Allergic treatment; Dendritic cell; Adoptive cell transfer
Issue Date
2021-06
Publisher
Biomaterials
Citation
VOL 273, 120798
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 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.
URI
http://pubs.kist.re.kr/handle/201004/73121
ISSN
0142-9612
Appears in Collections:
KIST Publication > Article
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