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

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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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 language	English
Article number	120798
Journal	Biomaterials
Volume	273
DOIs	https://doi.org/10.1016/j.biomaterials.2021.120798
Publication status	Published - 2021 Jun

Bibliographical note

Funding Information:
This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government ( 2020R1I1A2075393 to J.K.H., 2020R1I1A1A01072499 to B.K., 2020M3A9I4038662 to M.J., and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute , and the Ministry of Health & Welfare . This research was also supported by grants from Korea University , Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program ( 2E31091 ) of KIST . This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program ( IITP-2021-0-01819 ) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication.

Funding Information:
We would like to thank Woo Jeung Song (Department of Medicine, Major in Medical Genetics, Graduate School, Hanyang University) for off-target analysis based on a NGS method. This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government (2020R1I1A2075393 to J.K.H. 2020R1I1A1A01072499 to B.K. 2020M3A9I4038662 to M.J. and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute, and the Ministry of Health & Welfare. This research was also supported by grants from Korea University, Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program (2E31091) of KIST. This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program (IITP-2021-0-01819) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

Adoptive cell therapies
Allergies
CRISPR
Dendritic cells
Vacuolar protein sorting 37

ASJC Scopus subject areas

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

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10.1016/j.biomaterials.2021.120798

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@article{bc4dad7016f744f0ba42c925daa45742,

title = "A novel therapeutic modality using CRISPR-engineered dendritic cells to treat allergies",

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{\"i}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.",

keywords = "Adoptive cell therapies, Allergies, CRISPR, Dendritic cells, Vacuolar protein sorting 37",

author = "Byoungjae Kim and Lee, {Young Eun} and Yeon, {Ji Woo} and Go, {Ga Yeon} and Junhyoung Byun and Kijeong Lee and Lee, {Hyomin K.} and Hur, {Junho K.} and Mihue Jang and Kim, {Tae Hoon}",

note = "Funding Information: This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government ( 2020R1I1A2075393 to J.K.H., 2020R1I1A1A01072499 to B.K., 2020M3A9I4038662 to M.J., and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute , and the Ministry of Health & Welfare . This research was also supported by grants from Korea University , Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program ( 2E31091 ) of KIST . This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program ( IITP-2021-0-01819 ) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication. Funding Information: We would like to thank Woo Jeung Song (Department of Medicine, Major in Medical Genetics, Graduate School, Hanyang University) for off-target analysis based on a NGS method. This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government (2020R1I1A2075393 to J.K.H. 2020R1I1A1A01072499 to B.K. 2020M3A9I4038662 to M.J. and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute, and the Ministry of Health & Welfare. This research was also supported by grants from Korea University, Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program (2E31091) of KIST. This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program (IITP-2021-0-01819) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = jun,

doi = "10.1016/j.biomaterials.2021.120798",

language = "English",

volume = "273",

journal = "Biomaterials",

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AU - Lee, Young Eun

AU - Yeon, Ji Woo

AU - Go, Ga Yeon

AU - Byun, Junhyoung

AU - Lee, Kijeong

AU - Lee, Hyomin K.

AU - Hur, Junho K.

AU - Jang, Mihue

AU - Kim, Tae Hoon

N1 - Funding Information: This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government ( 2020R1I1A2075393 to J.K.H., 2020R1I1A1A01072499 to B.K., 2020M3A9I4038662 to M.J., and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute , and the Ministry of Health & Welfare . This research was also supported by grants from Korea University , Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program ( 2E31091 ) of KIST . This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program ( IITP-2021-0-01819 ) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication. Funding Information: We would like to thank Woo Jeung Song (Department of Medicine, Major in Medical Genetics, Graduate School, Hanyang University) for off-target analysis based on a NGS method. This research was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government (2020R1I1A2075393 to J.K.H. 2020R1I1A1A01072499 to B.K. 2020M3A9I4038662 to M.J. and 2017R1A2B2003575 and 2020R1A2C1006398 to T.H.), as well as the Korea Health Technology R&D Project (HI17C0387 to T.H.), Korea Health Industry Development Institute, and the Ministry of Health & Welfare. This research was also supported by grants from Korea University, Korea University Medical Center, and Anam Hospital (Seoul, Republic of Korea), and by grants from internal program (2E31091) of KIST. This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program (IITP-2021-0-01819) supervised by the IITP(Institute for Information & communications Technology Planning & Evaluation)). The sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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