دورية أكاديمية
Characterization of Gene Alterations following Editing of the β-Globin Gene Locus in Hematopoietic Stem/Progenitor Cells.
| العنوان: | Characterization of Gene Alterations following Editing of the β-Globin Gene Locus in Hematopoietic Stem/Progenitor Cells. |
|---|---|
| المؤلفون: | Long J; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Biology Department, California State University, Northridge, Northridge, CA 91330, USA., Hoban MD; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Cooper AR; Molecular Biology Interdepartmental Ph.D. Program, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kaufman ML; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kuo CY; Division of Allergy and Immunology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Campo-Fernandez B; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Lumaquin D; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Hollis RP; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Wang X; Department of Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kohn DB; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA., Romero Z; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: zulemar@ucla.edu. |
| المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2018 Feb 07; Vol. 26 (2), pp. 468-479. Date of Electronic Publication: 2017 Nov 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| مواضيع طبية MeSH: | Gene Editing* , Genetic Variation*, Hematopoietic Stem Cells/*metabolism , beta-Globins/*genetics, Gene Conversion ; Gene Rearrangement ; Gene Targeting ; High-Throughput Nucleotide Sequencing ; Humans ; Nucleic Acid Amplification Techniques ; Translocation, Genetic |
| مستخلص: | The use of engineered nucleases combined with a homologous DNA donor template can result in targeted gene correction of the sickle cell disease mutation in hematopoietic stem and progenitor cells. However, because of the high homology between the adjacent human β- and δ-globin genes, off-target cleavage is observed at δ-globin when using some endonucleases targeted to the sickle mutation in β-globin. Introduction of multiple double-stranded breaks by endonucleases has the potential to induce intergenic alterations. Using a novel droplet digital PCR assay and high-throughput sequencing, we characterized the frequency of rearrangements between the β- and δ-globin paralogs when delivering these nucleases. Pooled CD34 + cells and colony-forming units from sickle bone marrow were treated with nuclease only or including a donor template and then analyzed for potential gene rearrangements. It was observed that, in pooled CD34 + cells and colony-forming units, the intergenic β-δ-globin deletion was the most frequent rearrangement, followed by inversion of the intergenic fragment, with the inter-chromosomal translocation as the least frequent. No rearrangements were observed when endonuclease activity was restricted to on-target β-globin cleavage. These findings demonstrate the need to develop site-specific endonucleases with high specificity to avoid unwanted gene alterations. (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.) |
| References: | Mol Ther Nucleic Acids. 2016;5:e351. (PMID: 28131278) Nat Rev Genet. 2016 May;17(5):300-12. (PMID: 27087594) Nat Med. 2006 Apr;12(4):401-9. (PMID: 16582916) Genet Med. 2010 Feb;12(2):61-76. (PMID: 20098328) Nature. 2005 Jun 2;435(7042):646-51. (PMID: 15806097) Nat Protoc. 2016 May;11(5):853-71. (PMID: 27031497) Nat Commun. 2017 Jan 09;8:13905. (PMID: 28067217) Genome Res. 2012 Mar;22(3):539-48. (PMID: 22183967) J Virol. 1999 Jul;73(7):5490-6. (PMID: 10364297) Mol Ther. 2015 Sep;23(9):1465-74. (PMID: 26080908) Anal Chem. 2011 Nov 15;83(22):8604-10. (PMID: 22035192) Nucleic Acids Res. 2013 Nov;41(20):9584-92. (PMID: 23939622) Genome Biol Evol. 2013;5(3):559-71. (PMID: 23431002) Mol Cells. 2015 Jun;38(6):475-81. (PMID: 25985872) Blood. 2015 Apr 23;125(17):2597-604. (PMID: 25733580) Hum Gene Ther. 2007 Apr;18(4):333-43. (PMID: 17411365) Mol Ther. 2013 Sep;21(9):1705-17. (PMID: 23857176) Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10620-5. (PMID: 19549848) Science. 2000 Apr 28;288(5466):669-72. (PMID: 10784449) Nat Rev Genet. 2010 Sep;11(9):636-46. (PMID: 20717154) Blood. 2003 Mar 15;101(6):2175-83. (PMID: 12411297) Mol Ther. 2016 Sep;24(9):1561-9. (PMID: 27406980) Nat Biotechnol. 2008 Jul;26(7):808-16. (PMID: 18587387) Cell Stem Cell. 2016 Apr 7;18(4):533-40. (PMID: 26877224) Blood. 2016 May 26;127(21):2525-35. (PMID: 27053532) Science. 2001 Dec 14;294(5550):2368-71. (PMID: 11743206) Curr Opin Oncol. 2009 Mar;21(2):158-61. (PMID: 19532018) N Engl J Med. 2003 Jan 16;348(3):255-6. (PMID: 12529469) J Clin Invest. 2013 Jul 1;:null. (PMID: 23863630) Blood. 2004 Oct 15;104(8):2281-90. (PMID: 15198957) Nature. 2014 Jun 12;510(7504):235-240. (PMID: 24870228) In Vitro Cell Dev Biol Plant. 2015;51(1):1-8. (PMID: 25774080) Genome Res. 2010 Jan;20(1):81-9. (PMID: 19952142) Nature. 1957 Aug 17;180(4581):326-8. (PMID: 13464827) Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2567-71. (PMID: 8146155) Blood. 2003 Dec 15;102(13):4312-9. (PMID: 12933581) Sci Rep. 2016 Jul 20;6:29831. (PMID: 27436510) |
| معلومات مُعتمدة: | R25 GM055052 United States GM NIGMS NIH HHS; T32 AI060567 United States AI NIAID NIH HHS; T32 GM007185 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: chromosomal rearrangement; endonucleases; off-target |
| المشرفين على المادة: | 0 (beta-Globins) |
| تواريخ الأحداث: | Date Created: 20171210 Date Completed: 20190212 Latest Revision: 20240922 |
| رمز التحديث: | 20240922 |
| مُعرف محوري في PubMed: | PMC5835144 |
| DOI: | 10.1016/j.ymthe.2017.11.001 |
| PMID: | 29221806 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1525-0024 |
|---|---|
| DOI: | 10.1016/j.ymthe.2017.11.001 |