Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9 - PubMed (original) (raw)
. 2015 Aug 6;17(2):213-20.
doi: 10.1016/j.stem.2015.07.001. Epub 2015 Jul 23.
Affiliations
- PMID: 26212079
- DOI: 10.1016/j.stem.2015.07.001
Free article
Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9
Chul-Yong Park et al. Cell Stem Cell. 2015.
Free article
Abstract
Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene, which encodes the blood coagulation factor VIII. Almost half of all severe hemophilia A cases result from two gross (140-kbp or 600-kbp) chromosomal inversions that involve introns 1 and 22 of the F8 gene, respectively. We derived induced pluripotent stem cells (iPSCs) from patients with these inversion genotypes and used CRISPR-Cas9 nucleases to revert these chromosomal segments back to the WT situation. We isolated inversion-corrected iPSCs with frequencies of up to 6.7% without detectable off-target mutations based on whole-genome sequencing or targeted deep sequencing. Endothelial cells differentiated from corrected iPSCs expressed the F8 gene and functionally rescued factor VIII deficiency in an otherwise lethal mouse model of hemophilia. Our results therefore provide a proof of principle for functional correction of large chromosomal rearrangements in patient-derived iPSCs and suggest potential therapeutic applications.
Copyright © 2015 Elsevier Inc. All rights reserved.
Similar articles
- Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs.
Park CY, Kim J, Kweon J, Son JS, Lee JS, Yoo JE, Cho SR, Kim JH, Kim JS, Kim DW. Park CY, et al. Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9253-8. doi: 10.1073/pnas.1323941111. Epub 2014 Jun 9. Proc Natl Acad Sci U S A. 2014. PMID: 24927536 Free PMC article. - Universal Correction of Blood Coagulation Factor VIII in Patient-Derived Induced Pluripotent Stem Cells Using CRISPR/Cas9.
Park CY, Sung JJ, Cho SR, Kim J, Kim DW. Park CY, et al. Stem Cell Reports. 2019 Jun 11;12(6):1242-1249. doi: 10.1016/j.stemcr.2019.04.016. Epub 2019 May 16. Stem Cell Reports. 2019. PMID: 31105049 Free PMC article. - In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs.
Wu Y, Hu Z, Li Z, Pang J, Feng M, Hu X, Wang X, Lin-Peng S, Liu B, Chen F, Wu L, Liang D. Wu Y, et al. Sci Rep. 2016 Jan 8;6:18865. doi: 10.1038/srep18865. Sci Rep. 2016. PMID: 26743572 Free PMC article. - Molecular genetics of coagulation factor VIII gene and hemophilia A.
Antonarakis SE. Antonarakis SE. Thromb Haemost. 1995 Jul;74(1):322-8. Thromb Haemost. 1995. PMID: 8578479 Review. - [Molecular genetics of hemophilia A].
De Brasi CD, Slavutsky IR, Larripa IB. De Brasi CD, et al. Medicina (B Aires). 1996;56(5 Pt 1):509-17. Medicina (B Aires). 1996. PMID: 9239887 Review. Spanish.
Cited by
- Identification of the Efficient Enhancer Elements in FVIII-Padua for Gene Therapy Study of Hemophilia A.
Xiao R, Chen Y, Hu Z, Tang Q, Wang P, Zhou M, Wu L, Liang D. Xiao R, et al. Int J Mol Sci. 2024 Mar 24;25(7):3635. doi: 10.3390/ijms25073635. Int J Mol Sci. 2024. PMID: 38612447 Free PMC article. - Activation of recombinases at specific DNA loci by zinc-finger domain insertions.
Mukhametzyanova L, Schmitt LT, Torres-Rivera J, Rojo-Romanos T, Lansing F, Paszkowski-Rogacz M, Hollak H, Brux M, Augsburg M, Schneider PM, Buchholz F. Mukhametzyanova L, et al. Nat Biotechnol. 2024 Jan 31. doi: 10.1038/s41587-023-02121-y. Online ahead of print. Nat Biotechnol. 2024. PMID: 38297187 - Parallelized engineering of mutational models using piggyBac transposon delivery of CRISPR libraries.
Nuttle X, Burt ND, Currall B, Moysés-Oliveira M, Mohajeri K, Bhavsar R, Lucente D, Yadav R, Tai DJC, Gusella JF, Talkowski ME. Nuttle X, et al. Cell Rep Methods. 2024 Jan 22;4(1):100672. doi: 10.1016/j.crmeth.2023.100672. Epub 2023 Dec 12. Cell Rep Methods. 2024. PMID: 38091988 Free PMC article. - Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.
Aslan C, Zolbanin NM, Faraji F, Jafari R. Aslan C, et al. Mol Biotechnol. 2023 Nov 27. doi: 10.1007/s12033-023-00932-7. Online ahead of print. Mol Biotechnol. 2023. PMID: 38012525 Review. - Non-viral and viral delivery systems for hemophilia A therapy: recent development and prospects.
Zangi AR, Amiri A, Pazooki P, Soltanmohammadi F, Hamishehkar H, Javadzadeh Y. Zangi AR, et al. Ann Hematol. 2024 May;103(5):1493-1511. doi: 10.1007/s00277-023-05459-0. Epub 2023 Nov 11. Ann Hematol. 2024. PMID: 37951852 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous