Abstract
Hemophilia A (HA) is caused by genetic mutations in the blood coagulation factor VIII (FVIII) gene. Genome-editing approaches can be used to target the mutated site itself in patient-derived induced pluripotent stem cells (iPSCs). However, these approaches can be hampered by difficulty in preparing thousands of editing platforms for each corresponding variant found in HA patients. Here, we report a universal approach to correct the various mutations in HA patient iPSCs by the targeted insertion of the FVIII gene into the human H11 site via CRISPR/Cas9. We derived corrected clones from two types of patient iPSCs with frequencies of up to 64% and 66%, respectively, without detectable unwanted off-target mutations. Moreover, we demonstrated that endothelial cells differentiated from the corrected iPSCs successfully secreted functional protein. This strategy may provide a universal therapeutic method for correcting all genetic variants found in HA patients. Hemophilia A (HA) is caused by various genetic mutations within the blood coagulation factor VIII (FVIII) gene. In this article, Kim and colleagues attempt the targeted insertion of the FVIII gene into the human H11 site in two types of HA patient iPSCs. This approach may offer a universal therapeutic method for correcting all genetic variants found in HA patients.
| Original language | English |
|---|---|
| Pages (from-to) | 1242-1249 |
| Number of pages | 8 |
| Journal | Stem Cell Reports |
| Volume | 12 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2019 Jun 11 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology
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Universal Correction of Blood Coagulation Factor VIII in Patient-Derived Induced Pluripotent Stem Cells Using CRISPR/Cas9. / Park, Chul Yong; Sung, Jin Jea; Cho, Sung Rae; Kim, Jongwan; Kim, Dong Wook.
In: Stem Cell Reports, Vol. 12, No. 6, 11.06.2019, p. 1242-1249.Research output: Contribution to journal › Article
TY - JOUR
T1 - Universal Correction of Blood Coagulation Factor VIII in Patient-Derived Induced Pluripotent Stem Cells Using CRISPR/Cas9
AU - Park, Chul Yong
AU - Sung, Jin Jea
AU - Cho, Sung Rae
AU - Kim, Jongwan
AU - Kim, Dong Wook
PY - 2019/6/11
Y1 - 2019/6/11
N2 - Hemophilia A (HA) is caused by genetic mutations in the blood coagulation factor VIII (FVIII) gene. Genome-editing approaches can be used to target the mutated site itself in patient-derived induced pluripotent stem cells (iPSCs). However, these approaches can be hampered by difficulty in preparing thousands of editing platforms for each corresponding variant found in HA patients. Here, we report a universal approach to correct the various mutations in HA patient iPSCs by the targeted insertion of the FVIII gene into the human H11 site via CRISPR/Cas9. We derived corrected clones from two types of patient iPSCs with frequencies of up to 64% and 66%, respectively, without detectable unwanted off-target mutations. Moreover, we demonstrated that endothelial cells differentiated from the corrected iPSCs successfully secreted functional protein. This strategy may provide a universal therapeutic method for correcting all genetic variants found in HA patients. Hemophilia A (HA) is caused by various genetic mutations within the blood coagulation factor VIII (FVIII) gene. In this article, Kim and colleagues attempt the targeted insertion of the FVIII gene into the human H11 site in two types of HA patient iPSCs. This approach may offer a universal therapeutic method for correcting all genetic variants found in HA patients.
AB - Hemophilia A (HA) is caused by genetic mutations in the blood coagulation factor VIII (FVIII) gene. Genome-editing approaches can be used to target the mutated site itself in patient-derived induced pluripotent stem cells (iPSCs). However, these approaches can be hampered by difficulty in preparing thousands of editing platforms for each corresponding variant found in HA patients. Here, we report a universal approach to correct the various mutations in HA patient iPSCs by the targeted insertion of the FVIII gene into the human H11 site via CRISPR/Cas9. We derived corrected clones from two types of patient iPSCs with frequencies of up to 64% and 66%, respectively, without detectable unwanted off-target mutations. Moreover, we demonstrated that endothelial cells differentiated from the corrected iPSCs successfully secreted functional protein. This strategy may provide a universal therapeutic method for correcting all genetic variants found in HA patients. Hemophilia A (HA) is caused by various genetic mutations within the blood coagulation factor VIII (FVIII) gene. In this article, Kim and colleagues attempt the targeted insertion of the FVIII gene into the human H11 site in two types of HA patient iPSCs. This approach may offer a universal therapeutic method for correcting all genetic variants found in HA patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=85066748025&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2019.04.016
DO - 10.1016/j.stemcr.2019.04.016
M3 - Article
C2 - 31105049
AN - SCOPUS:85066748025
VL - 12
SP - 1242
EP - 1249
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 6
ER -