TALEN mediated gene editing in a mouse model of Fanconi anemia.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 04 2020
Historique:
received: 30 05 2019
accepted: 28 02 2020
entrez: 26 4 2020
pubmed: 26 4 2020
medline: 22 12 2020
Statut: epublish

Résumé

The promising ability to genetically modify hematopoietic stem and progenitor cells by precise gene editing remains challenging due to their sensitivity to in vitro manipulations and poor efficiencies of homologous recombination. This study represents the first evidence of implementing a gene editing strategy in a murine safe harbor locus site that phenotypically corrects primary cells from a mouse model of Fanconi anemia A. By means of the co-delivery of transcription activator-like effector nucleases and a donor therapeutic FANCA template to the Mbs85 locus, we achieved efficient gene targeting (23%) in mFA-A fibroblasts. This resulted in the phenotypic correction of these cells, as revealed by the reduced sensitivity of these cells to mitomycin C. Moreover, robust evidence of targeted integration was observed in murine wild type and FA-A hematopoietic progenitor cells, reaching mean targeted integration values of 21% and 16% respectively, that were associated with the phenotypic correction of these cells. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy into the mMbs85 locus, ortholog to the well-validated hAAVS1, constituting the first study of gene editing in mHSC with TALEN, that sets the basis for the use of a new safe harbor locus in mice.

Identifiants

pubmed: 32332829
doi: 10.1038/s41598-020-63971-z
pii: 10.1038/s41598-020-63971-z
pmc: PMC7181878
doi:

Substances chimiques

Transcription Activator-Like Effector Nucleases EC 3.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6997

Références

Bagby, G. Recent advances in understanding hematopoiesis in Fanconi Anemia. F1000Res 7, 105, https://doi.org/10.12688/f1000research.13213.1 (2018).
doi: 10.12688/f1000research.13213.1 pubmed: 29399332 pmcid: 5785713
Knies, K. et al. Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia. J Clin Invest 127, 3013–3027, https://doi.org/10.1172/JCI92069 (2017).
doi: 10.1172/JCI92069 pubmed: 28691929 pmcid: 5531404
Auerbach, A. D. Fanconi anemia and its diagnosis. Mutat Res 668, 4–10, https://doi.org/10.1016/j.mrfmmm.2009.01.013 (2009).
doi: 10.1016/j.mrfmmm.2009.01.013 pubmed: 19622403 pmcid: 2742943
Schneider, M., Chandler, K., Tischkowitz, M. & Meyer, S. Fanconi anaemia: genetics, molecular biology, and cancer - implications for clinical management in children and adults. Clin Genet 88, 13–24, https://doi.org/10.1111/cge.12517 (2015).
doi: 10.1111/cge.12517 pubmed: 25307146
Tischkowitz, M. D. & Hodgson, S. V. Fanconi anaemia. J Med Genet 40, 1–10 (2003).
doi: 10.1136/jmg.40.1.1
Ceccaldi, R. et al. Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells. Cell Stem Cell 11, 36–49, https://doi.org/10.1016/j.stem.2012.05.013 (2012).
doi: 10.1016/j.stem.2012.05.013 pubmed: 22683204 pmcid: 3392433
Kelly, P. F. et al. Stem cell collection and gene transfer in Fanconi anemia. Mol Ther 15, 211–219, https://doi.org/10.1038/sj.mt.6300033 (2007).
doi: 10.1038/sj.mt.6300033 pubmed: 17164793
Galimi, F. et al. Gene therapy of Fanconi anemia: preclinical efficacy using lentiviral vectors. Blood 100, 2732–2736, https://doi.org/10.1182/blood-2002-04-1245 (2002).
doi: 10.1182/blood-2002-04-1245 pubmed: 12351379
Jacome, A. et al. Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients. Mol Ther 17, 1083–1092, https://doi.org/10.1038/mt.2009.26 (2009).
doi: 10.1038/mt.2009.26 pubmed: 19277017 pmcid: 2835196
Muller, L. U. et al. Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells. Mol Ther 16, 1154–1160, https://doi.org/10.1038/mt.2008.67 (2008).
doi: 10.1038/mt.2008.67 pubmed: 28178472
Becker, P. S. et al. Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector. Gene Ther 17, https://doi.org/10.1038/gt.2010.62 (2010).
Gonzalez-Murillo, A. et al. Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with Fanconi anemia. Hum Gene Ther 21, 623–630, https://doi.org/10.1089/hum.2009.141 (2010).
doi: 10.1089/hum.2009.141 pubmed: 20001454
Molina-Estevez, F. J. et al. Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs. Curr Gene Ther 15, 550–562, https://doi.org/10.2174/1566523215666150929110903 (2015).
doi: 10.2174/1566523215666150929110903 pubmed: 26415575
Navarro, S., Rio, P. & Bueren, J. Perspectives on gene therapy for Fanconi anemia. Exper Opinion on Orphan Durgs 3, 1–12 (2015).
doi: 10.1517/21678707.2015.1084714
Tolar, J. et al. Stem cell gene therapy for fanconi anemia: report from the 1st international Fanconi anemia gene therapy working group meeting. Mol Ther 19, 1193–1198, https://doi.org/10.1038/mt.2011.78 (2011).
doi: 10.1038/mt.2011.78 pubmed: 21540837 pmcid: 3129570
Tolar, J. et al. Gene therapy for Fanconi anemia: one step closer to the clinic. Hum Gene Ther 23, 141–144, https://doi.org/10.1089/hum.2011.237 (2012).
doi: 10.1089/hum.2011.237 pubmed: 22248350 pmcid: 3277737
Adair, J. E. et al. Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia. Curr Gene Ther 16, 338–348, https://doi.org/10.2174/1566523217666170119113029 (2017).
doi: 10.2174/1566523217666170119113029 pubmed: 28103787
Rio, P. et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat Med 25, 1396–1401, https://doi.org/10.1038/s41591-019-0550-z .
Bueren, J. A. et al. Advances in the gene therapy of monogenic blood cell diseases. Clin Genet, https://doi.org/10.1111/cge.13593 .
Casado, J. A. et al. A comprehensive strategy for the subtyping of Fanconi Anemia patients: conclusions from the Spanish Fanconi Anemia research network. J Med Genet 44, 241–249 (2007).
doi: 10.1136/jmg.2006.044719
Castella, M. et al. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations. Blood 117, 3759–3769, https://doi.org/10.1182/blood-2010-08-299917 (2011).
doi: 10.1182/blood-2010-08-299917 pubmed: 21273304 pmcid: 3083295
Mehta, P. A. & Tolar, J. In GeneReviews(R) (eds R. A. Pagon et al.) (1993).
Papapetrou, E. P. & Schambach, A. Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy. Mol Ther 24, 678–684, https://doi.org/10.1038/mt.2016.38 (2016).
doi: 10.1038/mt.2016.38 pubmed: 26867951 pmcid: 4886940
Sadelain, M., Papapetrou, E. P. & Bushman, F. D. Safe harbours for the integration of new DNA in the human genome. Nat Rev Cancer 12, 51–58, https://doi.org/10.1038/nrc3179 (2011).
doi: 10.1038/nrc3179 pubmed: 22129804
Diez, B. et al. Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients. EMBO Mol Med, https://doi.org/10.15252/emmm.201707540 (2017).
Rio, P. et al. Targeted gene therapy and cell reprogramming in Fanconi anemia. EMBO Mol Med 6, 835–848, https://doi.org/10.15252/emmm.201303374 (2014).
doi: 10.15252/emmm.201303374 pubmed: 24859981 pmcid: 4203359
Kotin, R. M., Linden, R. M. & Berns, K. I. Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J 11, 5071–5078 (1992).
doi: 10.1002/j.1460-2075.1992.tb05614.x
DeKelver, R. C. et al. Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Res 20, 1133–1142, https://doi.org/10.1101/gr.106773.110 (2010).
doi: 10.1101/gr.106773.110 pubmed: 20508142 pmcid: 2909576
Ramachandra, C. J. et al. Efficient recombinase-mediated cassette exchange at the AAVS1 locus in human embryonic stem cells using baculoviral vectors. Nucleic Acids Res 39, e107, https://doi.org/10.1093/nar/gkr409 (2011).
doi: 10.1093/nar/gkr409 pubmed: 21685448 pmcid: 3167641
Zou, J. et al. Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting. Blood 117, 5561–5572, https://doi.org/10.1182/blood-2010-12-328161 (2011).
doi: 10.1182/blood-2010-12-328161 pubmed: 21411759 pmcid: 3110021
Smith, J. R. et al. Robust, persistent transgene expression in human embryonic stem cells is achieved with AAVS1-targeted integration. Stem Cells 26, 496–504, https://doi.org/10.1634/stemcells.2007-0039 (2008).
doi: 10.1634/stemcells.2007-0039 pubmed: 18024421
Hockemeyer, D. et al. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27, 851–857, https://doi.org/10.1038/nbt.1562 (2009).
doi: 10.1038/nbt.1562 pubmed: 19680244 pmcid: 4142824
Oceguera-Yanez, F. et al. Engineering the AAVS1 locus for consistent and scalable transgene expression in human iPSCs and their differentiated derivatives. Methods, https://doi.org/10.1016/j.ymeth.2015.12.012 (2016).
Lombardo, A. et al. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods 8, 861–869, https://doi.org/10.1038/nmeth.1674 (2011).
doi: 10.1038/nmeth.1674 pubmed: 21857672
van Rensburg, R. et al. Chromatin structure of two genomic sites for targeted transgene integration in induced pluripotent stem cells and hematopoietic stem cells. Gene Ther 20, 201–214, https://doi.org/10.1038/gt.2012.25 (2012).
doi: 10.1038/gt.2012.25 pubmed: 22436965 pmcid: 3661409
Dutheil, N. et al. Characterization of the mouse adeno-associated virus AAVS1 ortholog. J Virol 78, 8917–8921, https://doi.org/10.1128/JVI.78.16.8917-8921.2004 (2004).
doi: 10.1128/JVI.78.16.8917-8921.2004 pubmed: 15280500 pmcid: 479059
Henckaerts, E. & Linden, R. M. Adeno-associated virus: a key to the human genome? Future Virol 5, 555–574, https://doi.org/10.2217/fvl.10.48 (2010).
doi: 10.2217/fvl.10.48 pubmed: 21212830 pmcid: 3014576
Linden, R. M., Ward, P., Giraud, C., Winocour, E. & Berns, K. I. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 93, 11288–11294 (1996).
doi: 10.1073/pnas.93.21.11288
Linden, R. M., Winocour, E. & Berns, K. I. The recombination signals for adeno-associated virus site-specific integration. Proc Natl Acad Sci USA 93, 7966–7972 (1996).
doi: 10.1073/pnas.93.15.7966
Tan, I., Ng, C. H., Lim, L. & Leung, T. Phosphorylation of a novel myosin binding subunit of protein phosphatase 1 reveals a conserved mechanism in the regulation of actin cytoskeleton. J Biol Chem 276, 21209–21216, https://doi.org/10.1074/jbc.M102615200 (2001).
doi: 10.1074/jbc.M102615200 pubmed: 11399775
Corrigan-Curay, J. et al. Genome editing technologies: defining a path to clinic. Mol Ther 23, 796–806, https://doi.org/10.1038/mt.2015.54 (2015).
doi: 10.1038/mt.2015.54 pubmed: 25943494 pmcid: 4427885
Mussolino, C. et al. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res 39, 9283–9293, https://doi.org/10.1093/nar/gkr597 (2011).
doi: 10.1093/nar/gkr597 pubmed: 21813459 pmcid: 3241638
Fine, E. J., Cradick, T. J., Zhao, C. L., Lin, Y. & Bao, G. An online bioinformatics tool predicts zinc finger and TALE nuclease off-target cleavage. Nucleic Acids Res 42, e42, https://doi.org/10.1093/nar/gkt1326 (2013).
doi: 10.1093/nar/gkt1326 pubmed: 24381193 pmcid: 3973315
Navarro, S. et al. Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1. Mol Ther 14, 525–535, https://doi.org/10.1016/j.ymthe.2006.05.018 (2006).
doi: 10.1016/j.ymthe.2006.05.018 pubmed: 16859999
Riviere, J. et al. Variable correction of Artemis deficiency by I-Sce1-meganuclease-assisted homologous recombination in murine hematopoietic stem cells. Gene Ther 21, 529–532, https://doi.org/10.1038/gt.2014.20 (2014).
doi: 10.1038/gt.2014.20 pubmed: 24622732
Branzei, D. & Foiani, M. Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9, 297–308, https://doi.org/10.1038/nrm2351 (2008).
doi: 10.1038/nrm2351 pubmed: 18285803
Schiroli, G. et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9, https://doi.org/10.1126/scitranslmed.aan0820 (2017).
Li, S. J., Luo, Y., Zhang, L. M., Yang, W. & Zhang, G. G. Targeted introduction and effective expression of hFIX at the AAVS1 locus in mesenchymal stem cells. Mol Med Rep 15, 1313–1318, https://doi.org/10.3892/mmr.2017.6131 (2017).
doi: 10.3892/mmr.2017.6131 pubmed: 28112377 pmcid: 5367337
Mizutani, T., Haga, H. & Kawabata, K. Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells. Data Brief 6, 793–798, https://doi.org/10.1016/j.dib.2015.12.053 (2016).
doi: 10.1016/j.dib.2015.12.053 pubmed: 26937449 pmcid: 4749938
Mizutani, T., Li, R., Haga, H. & Kawabata, K. Transgene integration into the human AAVS1 locus enhances myosin II-dependent contractile force by reducing expression of myosin binding subunit 85. Biochem Biophys Res Commun 465, 270–274, https://doi.org/10.1016/j.bbrc.2015.08.018 (2015).
doi: 10.1016/j.bbrc.2015.08.018 pubmed: 26260320
Ordovas, L. et al. Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition. Stem Cell Reports 5, 918–931, https://doi.org/10.1016/j.stemcr.2015.09.004 (2015).
doi: 10.1016/j.stemcr.2015.09.004 pubmed: 26455413 pmcid: 4649136
Dreyer, A. K. et al. TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells. Biomaterials 69, 191–200, https://doi.org/10.1016/j.biomaterials.2015.07.057 (2015).
doi: 10.1016/j.biomaterials.2015.07.057 pubmed: 26295532
Gross, M. et al. Reverse mosaicism in Fanconi anemia: natural gene therapy via molecular self-correction. Cytogenet Genome Res 98, 126–135 (2002).
doi: 10.1159/000069805
Soulier, J. et al. Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 105, 1329–1336, https://doi.org/10.1182/blood-2004-05-1852 (2005).
doi: 10.1182/blood-2004-05-1852 pubmed: 15383454
Gregory, J. J. Jr. et al. Somatic mosaicism in Fanconi anemia: evidence of genotypic reversion in lymphohematopoietic stem cells. Proc Natl Acad Sci USA 98, 2532–2537, https://doi.org/10.1073/pnas.051609898 (2001).
doi: 10.1073/pnas.051609898 pubmed: 11226273
Waisfisz, Q. et al. Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism. Nat Genet 22, 379–383, https://doi.org/10.1038/11956 (1999).
doi: 10.1038/11956 pubmed: 10431244
Mankad, A. et al. Natural gene therapy in monozygotic twins with Fanconi anemia. Blood 107, 3084–3090, https://doi.org/10.1182/blood-2005-07-2638 (2006).
doi: 10.1182/blood-2005-07-2638 pubmed: 16397136 pmcid: 1895746
Lo Ten Foe, J. R. et al. Somatic mosaicism in Fanconi anemia: molecular basis and clinical significance. Eur J Hum Genet 5, 137–148 (1997).
doi: 10.1159/000484749
Rio, P. et al. Engraftment and in vivo proliferation advantage of gene corrected mobilized CD34+ cells from Fanconi anemia patients. Blood, https://doi.org/10.1182/blood-2017-03-774174 (2017).
Holkers, M. et al. Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 41, e63, https://doi.org/10.1093/nar/gks1446 (2013).
doi: 10.1093/nar/gks1446 pubmed: 23275534
Mock, U. et al. Novel lentiviral vectors with mutated reverse transcriptase for mRNA delivery of TALE nucleases. Sci Rep 4, 6409, https://doi.org/10.1038/srep06409 (2014).
doi: 10.1038/srep06409 pubmed: 25230987 pmcid: 4166709
Liu, J., Gaj, T., Patterson, J. T., Sirk, S. J. & Barbas, C. F. 3rd Cell-penetrating peptide-mediated delivery of TALEN proteins via bioconjugation for genome engineering. PLoS One 9, e85755, https://doi.org/10.1371/journal.pone.0085755 (2014).
doi: 10.1371/journal.pone.0085755 pubmed: 24465685 pmcid: 3896395
Cai, Y., Bak, R. O. & Mikkelsen, J. G. Targeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases. Elife 3, e01911 (2014).
doi: 10.7554/eLife.01911
Nakanishi, K. et al. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc Natl Acad Sci USA 102, 1110–1115, https://doi.org/10.1073/pnas.0407796102 (2005).
doi: 10.1073/pnas.0407796102 pubmed: 15650050
Adamo, A. et al. Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39, 25–35, https://doi.org/10.1016/j.molcel.2010.06.026 (2010).
doi: 10.1016/j.molcel.2010.06.026 pubmed: 20598602
Cheng, N. C. et al. Mice with a targeted disruption of the Fanconi anemia homolog Fanca. Hum Mol Genet 9, 1805–1811 (2000).
doi: 10.1093/hmg/9.12.1805
Rio, P. et al. In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice. Blood 100, 2032–2039 (2002).
doi: 10.1182/blood.V100.6.2032
Rahman, S. H. et al. Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model. PLoS Genet 11, e1005239, https://doi.org/10.1371/journal.pgen.1005239 (2015).
doi: 10.1371/journal.pgen.1005239 pubmed: 26000857 pmcid: 4441453
Bednarski, C., Tomczak, K., Vom Hovel, B., Weber, W. M. & Cathomen, T. Targeted Integration of a Super-Exon into the CFTR Locus Leads to Functional Correction of a Cystic Fibrosis Cell Line Model. PLoS One 11, e0161072, https://doi.org/10.1371/journal.pone.0161072 (2016).
doi: 10.1371/journal.pone.0161072 pubmed: 27526025 pmcid: 4985144
Koo, T., Lee, J. & Kim, J. S. Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9. Mol Cells 38, 475–481, https://doi.org/10.14348/molcells.2015.0103 (2015).
doi: 10.14348/molcells.2015.0103 pubmed: 25985872 pmcid: 4469905
Hendel, A., Fine, E. J., Bao, G. & Porteus, M. H. Quantifying on- and off-target genome editing. Trends Biotechnol 33, 132–140, https://doi.org/10.1016/j.tibtech.2014.12.001 (2015).
doi: 10.1016/j.tibtech.2014.12.001 pubmed: 25595557 pmcid: 4308725
Mussolino, C. et al. TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res 42, 6762–6773, https://doi.org/10.1093/nar/gku305 (2014).
doi: 10.1093/nar/gku305 pubmed: 24792154 pmcid: 4041469
Almarza, E. et al. Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy. Mol Ther 15, 1487–1494, https://doi.org/10.1038/sj.mt.6300213 (2007).
doi: 10.1038/sj.mt.6300213 pubmed: 17534266
Cornu, T. I., Mussolino, C. & Cathomen, T. Refining strategies to translate genome editing to the clinic. Nat Med 23, 415–423, https://doi.org/10.1038/nm.4313 (2017).
doi: 10.1038/nm.4313 pubmed: 28388605
Mock, U. et al. mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5. Nucleic Acids Res 43, 5560–5571, https://doi.org/10.1093/nar/gkv469 (2015).
doi: 10.1093/nar/gkv469 pubmed: 25964300 pmcid: 4477672
Poirot, L. et al. Multiplex Genome-Edited T-cell Manufacturing Platform for “Off-the-Shelf” Adoptive T-cell Immunotherapies. Cancer Res 75, 3853–3864, https://doi.org/10.1158/0008-5472.CAN-14-3321 (2015).
doi: 10.1158/0008-5472.CAN-14-3321 pubmed: 26183927
Qasim, W. et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med 9, https://doi.org/10.1126/scitranslmed.aaj2013 (2017).
De Ravin, S. S. et al. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease. Nat Biotechnol 34, 424–429, https://doi.org/10.1038/nbt.3513 (2016).
doi: 10.1038/nbt.3513 pubmed: 26950749 pmcid: 4824656
Wang, J. et al. Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors. Nat Biotechnol 33, 1256–1263, https://doi.org/10.1038/nbt.3408 (2015).
doi: 10.1038/nbt.3408 pubmed: 26551060 pmcid: 4842001
Gundry, M. C. et al. Highly Efficient Genome Editing of Murine and Human Hematopoietic Progenitor Cells by CRISPR/Cas9. Cell Rep 17, 1453–1461, https://doi.org/10.1016/j.celrep.2016.09.092 (2016).
doi: 10.1016/j.celrep.2016.09.092 pubmed: 27783956 pmcid: 5087995
Navarro, S. et al. Generation of iPSCs from genetically corrected Brca2 hypomorphic cells: implications in cell reprogramming and stem cell therapy. Stem Cells 32, 436–446, https://doi.org/10.1002/stem.1586 (2014).
doi: 10.1002/stem.1586 pubmed: 24420904
Naviaux, R. K., Costanzi, E., Haas, M. & Verma, I. M. The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses. J Virol 70, 5701–5705 (1996).
doi: 10.1128/JVI.70.8.5701-5705.1996
Morbitzer, R., Elsaesser, J., Hausner, J. & Lahaye, T. Assembly of custom TALE-type DNA binding domains by modular cloning. Nucleic Acids Res 39, 5790–5799, https://doi.org/10.1093/nar/gkr151 (2011).
doi: 10.1093/nar/gkr151 pubmed: 21421566 pmcid: 3141260
Charrier, S. et al. Quantification of lentiviral vector copy numbers in individual hematopoietic colony-forming cells shows vector dose-dependent effects on the frequency and level of transduction. Gene Ther 18, 479–487, https://doi.org/10.1038/gt.2010.163 (2011).
doi: 10.1038/gt.2010.163 pubmed: 21160533
Raya, A. et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460, 53–59, https://doi.org/10.1038/nature08129 (2009).
doi: 10.1038/nature08129 pubmed: 19483674 pmcid: 2720823
Lin, Y. et al. SAPTA: a new design tool for improving TALE nuclease activity. Nucleic Acids Res 42, e47, https://doi.org/10.1093/nar/gkt1363 (2014).
doi: 10.1093/nar/gkt1363 pubmed: 24442582 pmcid: 3973288
Magoc, T. & Salzberg, S. L. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27, 2957–2963, https://doi.org/10.1093/bioinformatics/btr507 (2011).
doi: 10.1093/bioinformatics/btr507 pubmed: 21903629 pmcid: 21903629

Auteurs

Maria José Pino-Barrio (MJ)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.

Yari Giménez (Y)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.

Mariela Villanueva (M)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.

Marcus Hildenbeutel (M)

Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79106, Freiburg, Germany.
Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, 79106, Freiburg, Germany.

Rebeca Sánchez-Dominguez (R)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.

Sandra Rodríguez-Perales (S)

Molecular Cytogenetics Group, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernandez Almagro, 3, 28029, Madrid, Spain.

Roser Pujol (R)

Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.
Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.

Jordi Surrallés (J)

Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.
Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.

Paula Río (P)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain.

Toni Cathomen (T)

Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79106, Freiburg, Germany.
Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, 79106, Freiburg, Germany.
Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Claudio Mussolino (C)

Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, 79106, Freiburg, Germany.
Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, 79106, Freiburg, Germany.

Juan Antonio Bueren (JA)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain. juan.bueren@ciemat.es.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain. juan.bueren@ciemat.es.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain. juan.bueren@ciemat.es.

Susana Navarro (S)

Division of Hematopoietic Innovative Therapies, CIEMAT/CIBERER, 28040, Madrid, Spain. s.navarro@ciemat.es.
Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), 28040, Madrid, Spain. s.navarro@ciemat.es.
Center for Biomedical Network Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain. s.navarro@ciemat.es.

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