CRISPR/Cas9-Mediated Correction of the FANCD1 Gene in Primary Patient Cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373803" target="_blank" >RIV/00216208:11130/17:10373803 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.3390/ijms18061269" target="_blank" >https://doi.org/10.3390/ijms18061269</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms18061269" target="_blank" >10.3390/ijms18061269</a>

Result language

angličtina

Original language name

CRISPR/Cas9-Mediated Correction of the FANCD1 Gene in Primary Patient Cells

Original language description

Fanconi anemia (FA) is an inherited condition characterized by impaired DNA repair, physical anomalies, bone marrow failure, and increased incidence of malignancy. Gene editing holds great potential to precisely correct the underlying genetic cause such that gene expression remains under the endogenous control mechanisms. This has been accomplished to date only in transformed cells or their reprogrammed induced pluripotent stem cell counterparts; however, it has not yet been reported in primary patient cells. Here we show the ability to correct a mutation in Fanconi anemia D1 (FANCD1) primary patient fibroblasts. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system was employed to target and correct a FANCD1 gene deletion. Homologous recombination using an oligonucleotide donor was achieved and a pure population of modified cells was obtained by using inhibitors of poly adenosine diphosphate-ribose polymerase (poly ADP-ribose polymerase). FANCD1 function was restored and we did not observe any promiscuous cutting of the CRISPR/Cas9 at off target sites. This consideration is crucial in the context of the pre-malignant FA phenotype. Altogether we show the ability to correct a patient mutation in primary FANCD1 cells in a precise manner. These proof of principle studies support expanded application of gene editing for FA.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/GJ17-04941Y" target="_blank" >GJ17-04941Y: Development of gene-editing tools for correction and validation of mutations cuasative of monogenic hematopoietic disorders</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

18

Issue of the periodical within the volume

6

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

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UT code for WoS article

000404581500167

EID of the result in the Scopus database

2-s2.0-85020936376