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

Byoungjae Kim, Young Eun Lee, Ji Woo Yeon, Ga Yeon Go, Junhyoung Byun, Kijeong Lee, Hyomin K. Lee, Junho K. Hur, Mihue Jang, Tae Hoon Kim

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Article number120798
JournalBiomaterials
Volume273
DOIs
Publication statusPublished - 2021 Jun

Keywords

  • Adoptive cell therapies
  • Allergies
  • CRISPR
  • Dendritic cells
  • Vacuolar protein sorting 37

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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