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

doi:10.1016/j.biomaterials.2021.120798

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

Biomaterials. 2021 Jun:273:120798. doi: 10.1016/j.biomaterials.2021.120798. Epub 2021 Apr 10.

Authors

Byoungjae Kim¹, Young Eun Lee², Ji Woo Yeon³, Ga-Yeon Go⁴, Junhyoung Byun³, Kijeong Lee³, Hyomin K Lee⁵, Junho K Hur⁶, Mihue Jang⁷, Tae Hoon Kim⁸

Affiliations

¹ Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, 02841, Republic of Korea; Neuroscience Research Institute, Korea University, College of Medicine, Seoul, 02841, Republic of Korea.
² Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea; Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
³ Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
⁴ Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea.
⁵ Department of Medicine, Major in Medical Genetics, Graduate School, Hanyang University, Seoul, 04763, Republic of Korea.
⁶ Department of Genetics, College of Medicine, Hanyang University, Seoul, 04763, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea.
⁷ Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 02792, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: mihue@kist.re.kr.
⁸ Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, 02841, Republic of Korea. Electronic address: doctorthk@gmail.com.

PMID: 33895493
DOI: 10.1016/j.biomaterials.2021.120798

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 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.

Keywords: Adoptive cell therapies; Allergies; CRISPR; Dendritic cells; Vacuolar protein sorting 37.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Dermatophagoides
Clustered Regularly Interspaced Short Palindromic Repeats*
Dendritic Cells
Humans
Hypersensitivity* / therapy
Mice
Th2 Cells

Substances

Antigens, Dermatophagoides