Genome-wide CRISPR/Cas9 knockout screening revealed genes
involved in CD20 regulation.

a 2023

Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation.

DOSTÁLOVÁ, Lenka; Aneta LEDEREROVÁ; Helena PESCHELOVÁ; Tomáš LOJA; Michal ŠMÍDA et. al.

Základní údaje

Originální název

Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation.

Autoři

DOSTÁLOVÁ, Lenka (203 Česká republika, domácí); Aneta LEDEREROVÁ (203 Česká republika, domácí); Helena PESCHELOVÁ (203 Česká republika, domácí); Tomáš LOJA (703 Slovensko, domácí) a Michal ŠMÍDA (203 Česká republika, garant, domácí)

Vydání

CRISPR as a research tool in cancer and regenerative medicine, Stockholm, Švédsko, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švédsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14740/23:00132784

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

CD20 antigen; mAb therapy; rituximab

Štítky

NÚVR_CEITEC, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 4. 2024 10:11, Mgr. Eva Dubská

Anotace

V originále

CD20 antigen has been used as a target of monoclonal antibodies (mAb) such as rituximab (RTX) in the therapy of B-cell malignancies for more than two decades. However, malignant B cells downregulate CD20 on their surface, resulting in mAb resistance and therapy failure. Therefore, it is crucial to investigate the CD20 regulation to enhance the efficacy of anti CD20 mAb. This project aimed to perform CRISPR/Cas9 knockout screening to identify genes whose disruption restores CD20 surface expression. To create a model mimicking the situation in patients who have developed resistance to mAb therapy, we generated RTX-resistant CD20-low B-cell line by chronic exposure to rituximab. These cells were transduced by the GeCKO lentiviral library to obtain a collection of single-gene knockouts. After 2.5-week cultivation, the top 5% of cells with the highest expression of CD20 were sorted out. Using next-generation sequencing, we identified gene knockouts responsible for CD20 upregulation.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

MUNI/A/1224/2022, interní kód MU

Název: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit X

Investor: Masarykova univerzita, Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit X

Přiložené soubory

CRISPR_Symposium2023_Abstracts.pdf

Citovat

DOSTÁLOVÁ, Lenka; Aneta LEDEREROVÁ; Helena PESCHELOVÁ; Tomáš LOJA a Michal ŠMÍDA. Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation. In CRISPR as a research tool in cancer and regenerative medicine, Stockholm, Švédsko. 2023.

@proceedings{2356319,
   author = {Dostálová, Lenka and Ledererová, Aneta and Peschelová, Helena and Loja, Tomáš and Šmída, Michal},
   booktitle = {CRISPR as a research tool in cancer and regenerative medicine, Stockholm, Švédsko},
   keywords = {CD20 antigen; mAb therapy; rituximab},
   language = {eng},
   title = {Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation.},
   url = {https://is.muni.cz/auth/publication/2356319/CRISPR_Symposium2023_Abstracts.pdf},
   year = {2023}
}

TY  - CONF
ID  - 2356319
AU  - Dostálová, Lenka - Ledererová, Aneta - Peschelová, Helena - Loja, Tomáš - Šmída, Michal
PY  - 2023
TI  - Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation.
KW  - CD20 antigen
KW  - mAb therapy
KW  - rituximab
UR  - https://is.muni.cz/auth/publication/2356319/CRISPR_Symposium2023_Abstracts.pdf
N2  - CD20 antigen has been used as a target of monoclonal antibodies (mAb) such as rituximab (RTX) in the therapy of B-cell malignancies for more than two decades. However, malignant B cells downregulate CD20 on their surface, resulting in mAb resistance and therapy failure. Therefore, it is crucial to investigate the CD20 regulation to enhance the efficacy of anti CD20 mAb. This project aimed to perform CRISPR/Cas9 knockout screening to identify genes whose disruption restores CD20 surface expression. To create a model mimicking the situation in patients who have developed resistance to mAb therapy, we generated RTX-resistant CD20-low B-cell line by chronic exposure to rituximab. These cells were transduced by the GeCKO lentiviral library to obtain a collection of single-gene knockouts. After 2.5-week cultivation, the top 5% of cells with the highest expression of CD20 were sorted out. Using next-generation sequencing, we identified gene knockouts responsible for CD20 upregulation.
ER  -

DOSTÁLOVÁ, Lenka; Aneta LEDEREROVÁ; Helena PESCHELOVÁ; Tomáš LOJA a Michal ŠMÍDA. Genome-wide CRISPR/Cas9 knockout screening revealed genes involved in CD20 regulation. In \textit{CRISPR as a research tool in cancer and regenerative medicine, Stockholm, Švédsko}. 2023.

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