Abstract
Hematopoietic stem cells (HSCs) can be isolated and collected from the body, genetically modified, and expanded ex vivo. The invention of innovative and powerful gene editing tools has provided researchers with great convenience in genetically modifying a wide range of cells, including hematopoietic stem and progenitor cells (HSPCs). In addition to being used to modify genes to study the functional role that specific genes play in the hematopoietic system, the application of gene editing platforms in HSCs is largely focused on the development of cell-based gene editing therapies to treat diseases such as immune deficiency disorders and inherited blood disorders. Here, we review the application of gene editing tools in HSPCs. In particular, we provide a broad overview of the development of gene editing tools, multiple strategies for the application of gene editing tools in HSPCs, and exciting clinical advances in HSPC gene editing therapies. We also outline the various challenges integral to clinical translation of HSPC gene editing and provide the possible corresponding solutions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aiuti A et al (2013) Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341:1233151
Angelucci E, Pilo F (2016) Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major. Ann N Y Acad Sci 1368:115–121. https://doi.org/10.1111/nyas.13027
Angelucci E et al (2014) Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica 99:811–820. https://doi.org/10.3324/haematol.2013.099747
Antony JS et al (2018) Gene correction of HBB mutations in CD34+ hematopoietic stem cells using Cas9 mRNA and ssODN donors. Mol Cell Pediatr 5:1–7
Anzalone AV et al (2019) Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576:149–157. https://doi.org/10.1038/s41586-019-1711-4
Anzalone AV, Koblan LW, Liu DR (2020) Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol 38:824–844
Azhagiri MKK, Babu P, Venkatesan V, Thangavel S (2021) Homology-directed gene-editing approaches for hematopoietic stem and progenitor cell gene therapy. Stem Cell Res Ther 12:1–12
Bae S, Park J, Kim JS (2014) Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30:1473–1475. https://doi.org/10.1093/bioinformatics/btu048
Bak RO, Porteus MH (2017) CRISPR-mediated integration of large gene cassettes using AAV donor vectors. Cell Rep 20:750–756. https://doi.org/10.1016/j.celrep.2017.06.064
Barriga F, RamÃrez P, Wietstruck A, Rojas N (2012) Hematopoietic stem cell transplantation: clinical use and perspectives. Biol Res 45:307–316
Bauer DE, Orkin SH (2011) Update on fetal hemoglobin gene regulation in hemoglobinopathies. Curr Opin Pediatr 23:1
Bauer DE, Orkin SH (2015) Hemoglobin switching’s surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev 33:62–70. https://doi.org/10.1016/j.gde.2015.08.001
Bauer DE et al (2013) An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342:253–257. https://doi.org/10.1126/science.1242088
Becker AJ, McCulloch EA, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452
Belfort M, Roberts RJ (1997) Homing endonucleases: keeping the house in order. Nucleic Acids Res 25:3379–3388
Biffi A et al (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341:1233158
Bischoff N, Wimberger S, Maresca M, Brakebusch C (2020) Improving precise CRISPR genome editing by small molecules: is there a magic potion? Cell 9:1318
Bogdanove AJ, Voytas DF (2011) TAL effectors: customizable proteins for DNA targeting. Science 333:1843–1846
Brendel C et al (2016) Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. J Clin Invest 126:3868–3878. https://doi.org/10.1172/JCI87885
Brendel C et al (2020) Preclinical evaluation of a novel lentiviral vector driving lineage-specific BCL11A knockdown for sickle cell gene therapy. Mol Ther Methods Clin Dev 17:589–600. https://doi.org/10.1016/j.omtm.2020.03.015
Bryder D, Rossi DJ, Weissman IL (2006) Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 169:338–346
Carroll D (2011) Genome engineering with zinc-finger nucleases. Genetics 188:773–782
Cartier N et al (2009) Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326:818–823
Chames P et al (2005) In vivo selection of engineered homing endonucleases using double-strand break induced homologous recombination. Nucleic Acids Res 33:e178–e178
Check E (2002) Regulators split on gene therapy as patient shows signs of cancer. Nature 419:545–546. https://doi.org/10.1038/419545a
Check E (2005) Gene therapy put on hold as third child develops cancer. Nature 433:561. https://doi.org/10.1038/433561a
Chen F et al (2011) High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat Methods 8:753–755
Chen PJ et al (2021) Enhanced prime editing systems by manipulating cellular determinants of editing outcomes. Cell 184:5635–5652.e5629. https://doi.org/10.1016/j.cell.2021.09.018
Christen F et al (2022) Modeling clonal hematopoiesis in umbilical cord blood cells by CRISPR/Cas9. Leukemia 36:1102–1110
Chylinski K, Makarova KS, Charpentier E, Koonin EV (2014) Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res 42:6091–6105
Cong L et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823
Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826
de Melo J, Blackshaw S (2018) In vivo electroporation of developing mouse retina. Methods Mol Biol 1715:101–111. https://doi.org/10.1007/978-1-4939-7522-8_8
Dever DP et al (2016) CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature 539:384–389. https://doi.org/10.1038/nature20134
Duarte RF et al (2019) Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant 54:1525–1552
Eichler F et al (2017) Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med 377:1630–1638
Enache OM et al (2020) Cas9 activates the p53 pathway and selects for p53-inactivating mutations. Nat Genet 52:662–668. https://doi.org/10.1038/s41588-020-0623-4
Ford C, Hamerton J, Barnes D, Loutit J (1956) Cytological identification of radiation-chimaeras. Nature 177:452–454
Fowler J, Wu A, Till J, McCulloch E, Siminovitch L (1967) The cellular composition of hematopoietic spleen colonies. J Cell Physiol 69:65–71
Frangoul H et al (2021) CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med 384:252–260
Fu Y-W et al (2021) Dynamics and competition of CRISPR–Cas9 ribonucleoproteins and AAV donor-mediated NHEJ, MMEJ and HDR editing. Nucleic Acids Res 49:969–985
Fu B et al (2022) CRISPR–Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia. Nat Med 1-8:1573
Gaj T, Gersbach CA, Barbas CF III (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31:397–405
Gaudelli NM et al (2017) Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage. Nature 551:464–471. https://doi.org/10.1038/nature24644
Gaudelli NM et al (2020) Directed evolution of adenine base editors with increased activity and therapeutic application. Nat Biotechnol 38:892–900. https://doi.org/10.1038/s41587-020-0491-6
Gehrke JM et al (2018) An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat Biotechnol 36:977–982. https://doi.org/10.1038/nbt.4199
Gentner B et al (2021) Hematopoietic stem-and progenitor-cell gene therapy for Hurler syndrome. N Engl J Med 385:1929–1940
Gomez-Ospina N et al (2019) Human genome-edited hematopoietic stem cells phenotypically correct mucopolysaccharidosis type I. Nat Commun 10:1–14
Goyal S et al (2022) Acute myeloid leukemia case after gene therapy for sickle cell disease. N Engl J Med 386:138–147
Gundry MC et al (2016) Highly efficient genome editing of murine and human hematopoietic progenitor cells by CRISPR/Cas9. Cell Rep 17:1453–1461
Gupta RM, Musunuru K (2014) Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest 124:4154–4161
Hacein-Bey-Abina S et al (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302:415–419. https://doi.org/10.1126/science.1088547
Hacein-Bey-Abina S et al (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118:3132–3142. https://doi.org/10.1172/JCI35700
Hao M, Qiao J, Qi H (2020) Current and emerging methods for the synthesis of single-stranded DNA. Genes 11:116
Hashimoto M, Takemoto T (2015) Electroporation enables the efficient mRNA delivery into the mouse zygotes and facilitates CRISPR/Cas9-based genome editing. Sci Rep 5:1–8
Hendel A et al (2015) Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat Biotechnol 33:985–989. https://doi.org/10.1038/nbt.3290
Horii T et al (2014) Validation of microinjection methods for generating knockout mice by CRISPR/Cas-mediated genome engineering. Sci Rep 4:4513. https://doi.org/10.1038/srep04513
Horvath P, Barrangou R (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167–170
Hsieh MM et al (2020) Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease. Blood Adv 4:2058–2063. https://doi.org/10.1182/bloodadvances.2019001330
Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157:1262–1278
Hu JH et al (2018) Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 556:57–63. https://doi.org/10.1038/nature26155
Iliakis G et al (2004) Mechanisms of DNA double strand break repair and chromosome aberration formation. Cytogenet Genome Res 104:14–20
Jacobson L, Simmons E, Marks E, Eldredge J (1951) Recovery from radiation injury. Science 113:510–511
Jinek M et al (2012) A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821
Kenjo E et al (2021) Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice. Nat Commun 12:7101. https://doi.org/10.1038/s41467-021-26714-w
Khan FA et al (2016) CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases. Oncotarget 7:52541
Kim Y-G, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci 93:1156–1160
Kim D et al (2015) Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods 12:237–243. https://doi.org/10.1038/nmeth.3284, 231 p following 243
Kleinstiver BP et al (2015) Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481–485. https://doi.org/10.1038/nature14592
Kleinstiver BP et al (2016) High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529:490–495. https://doi.org/10.1038/nature16526
Koblan LW et al (2018) Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol 36:843–846. https://doi.org/10.1038/nbt.4172
Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533:420–424. https://doi.org/10.1038/nature17946
Komor AC et al (2017) Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci Adv 3:eaao4774. https://doi.org/10.1126/sciadv.aao4774
Koniali L, Lederer CW, Kleanthous M (2021) Therapy development by genome editing of hematopoietic stem cells. Cell 10:1492
Kotterman MA, Chalberg TW, Schaffer DV (2015) Viral vectors for gene therapy: translational and clinical outlook. Annu Rev Biomed Eng 17:63–89. https://doi.org/10.1146/annurev-bioeng-071813-104938
Kumar P, Tan Y, Cahan P (2017) Understanding development and stem cells using single cell-based analyses of gene expression. Development 144:17–32
Landrum MJ et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980–D985. https://doi.org/10.1093/nar/gkt1113
Landrum MJ et al (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44:D862–D868. https://doi.org/10.1093/nar/gkv1222
Lawson KA, Meneses JJ, Pedersen RA (1986) Cell fate and cell lineage in the endoderm of the presomite mouse embryo, studied with an intracellular tracer. Dev Biol 115:325–339
Lee CS et al (2017) Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes Dis 4:43–63. https://doi.org/10.1016/j.gendis.2017.04.001
Leibowitz ML et al (2021) Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing. Nat Genet 53:895–905. https://doi.org/10.1038/s41588-021-00838-7
Liu KC et al (2014) Integrase-deficient lentivirus: opportunities and challenges for human gene therapy. Curr Gene Ther 14:352–364. https://doi.org/10.2174/1566523214666140825124311
Liu M et al (2019) Methodologies for improving HDR efficiency. Front Genet 9:691
Liu B et al (2020) Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. Nucleic Acids Res 48:517–532
Locatelli F, Merli P, Strocchio L (2016) Transplantation for thalassemia major: alternative donors. Curr Opin Hematol 23:515–523. https://doi.org/10.1097/MOH.0000000000000280
Mali P et al (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826
Mao AS, Mooney DJ (2015) Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci 112:14452–14459
Marktel S et al (2019) Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia. Nat Med 25:234–241
Mehta A, Merkel OM (2020) Immunogenicity of Cas9 protein. J Pharm Sci 109:62–67. https://doi.org/10.1016/j.xphs.2019.10.003
Mohsen MO, Zha L, Cabral-Miranda G, Bachmann MF (2017) Major findings and recent advances in virus-like particle (VLP)-based vaccines. Semin Immunol 34:123–132. https://doi.org/10.1016/j.smim.2017.08.014
Morgan RA, Gray D, Lomova A, Kohn DB (2017) Hematopoietic stem cell gene therapy: progress and lessons learned. Cell Stem Cell 21:574–590
Morgan MA, Galla M, Grez M, Fehse B, Schambach A (2021) Retroviral gene therapy in Germany with a view on previous experience and future perspectives. Gene Ther 28:494–512
Mu W et al (2019) In vitro transcribed sgRNA causes cell death by inducing interferon release. Protein Cell 10:461–465. https://doi.org/10.1007/s13238-018-0605-9
Muller-Sieburg CE, Whitlock CA, Weissman IL (1986) Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1lo hematopoietic stem cell. Cell 44:653–662
Muller-Sieburg CE, Sieburg HB, Bernitz JM, Cattarossi G (2012) Stem cell heterogeneity: implications for aging and regenerative medicine. Blood 119:3900–3907
Muruve DA (2004) The innate immune response to adenovirus vectors. Hum Gene Ther 15:1157–1166. https://doi.org/10.1089/hum.2004.15.1157
Nishimasu H et al (2018) Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 361:1259–1262. https://doi.org/10.1126/science.aas9129
Okamoto S, Amaishi Y, Maki I, Enoki T, Mineno J (2019) Highly efficient genome editing for single-base substitutions using optimized ssODNs with Cas9-RNPs. Sci Rep 9:1–11
Osawa M, Hanada K-I, Hamada H, Nakauchi H (1996) Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273:242–245
Paquet D et al (2016) Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature 533:125–129
Park H, Shin J, Choi H, Cho B, Kim J (2020) Valproic acid significantly improves CRISPR/Cas9-mediated gene editing. Cell 9:1447
Pattabhi S et al (2019) In vivo outcome of homology-directed repair at the HBB gene in HSC using alternative donor template delivery methods. Mol Ther Nucleic Acids 17:277–288
Pavel-Dinu M et al (2019) Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nat Commun 10:1–15
Pensado A, Seijo B, Sanchez A (2014) Current strategies for DNA therapy based on lipid nanocarriers. Expert Opin Drug Deliv 11:1721–1731. https://doi.org/10.1517/17425247.2014.935337
Piel FB (2016) The present and future global burden of the inherited disorders of hemoglobin. Hematol Oncol Clin North Am 30:327–341
Platt OS (2008) Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 358:1362–1369
Popescu NC, Zimonjic D, DiPaolo JA (1990) Viral integration, fragile sites, and proto-oncogenes in human neoplasia. Hum Genet 84:383–386. https://doi.org/10.1007/BF00195804
Post Y, Clevers H (2019) Defining adult stem cell function at its simplest: the ability to replace lost cells through mitosis. Cell Stem Cell 25:174–183. https://doi.org/10.1016/j.stem.2019.07.002
Quadros RM et al (2017) Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins. Genome Biol 18:1–15
Rai R et al (2020) Targeted gene correction of human hematopoietic stem cells for the treatment of Wiskott-Aldrich syndrome. Nat Commun 11:1–15
Ramirez CL et al (2008) Unexpected failure rates for modular assembly of engineered zinc fingers. Nat Methods 5:374–375
Ran F et al (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308
Ran FA et al (2015) In vivo genome editing using Staphylococcus aureus Cas9. Nature 520:186–191. https://doi.org/10.1038/nature14299
Remy S et al (2017) Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA into intact zygotes using electroporation. Sci Rep 7:1–13
Renaud J-B et al (2016) Improved genome editing efficiency and flexibility using modified oligonucleotides with TALEN and CRISPR-Cas9 nucleases. Cell Rep 14:2263–2272
Richter MF et al (2020) Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity (vol 15, pg 891, 2020). Nat Biotechnol 38:901–901. https://doi.org/10.1038/s41587-020-0562-8
Rissone A, Burgess SM (2018) Rare genetic blood disease modeling in zebrafish. Front Genet 9:348
Rothe M, Modlich U, Schambach A (2013) Biosafety challenges for use of lentiviral vectors in gene therapy. Curr Gene Ther 13:453–468. https://doi.org/10.2174/15665232113136660006
Sakata RC et al (2020) Base editors for simultaneous introduction of C-to-T and A-to-G mutations. Nat Biotechnol 38:865–869. https://doi.org/10.1038/s41587-020-0509-0
Salisbury-Ruf CT, Larochelle A (2021) Advances and obstacles in homology-mediated gene editing of hematopoietic stem cells. J Clin Med 10:513
Salsman J, Dellaire G (2017) Precision genome editing in the CRISPR era. Biochem Cell Biol 95:187–201
Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32:347–355
Scharenberg SG et al (2020) Engineering monocyte/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing. Nat Commun 11:1–14
Schiroli G et al (2019) Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell 24:551–565.e558. https://doi.org/10.1016/j.stem.2019.02.019
Scott T, Soemardy C, Morris KV (2020) Development of a facile approach for generating chemically modified CRISPR/Cas9 RNA. Mol Ther Nucleic Acids 19:1176–1185. https://doi.org/10.1016/j.omtn.2020.01.004
Seita J, Weissman IL (2010) Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med 2:640–653
Siminovitch L, McCulloch EA, Till JE (1963) The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol 62:327
Smith LG, Weissman IL, Heimfeld S (1991) Clonal analysis of hematopoietic stem-cell differentiation in vivo. Proc Natl Acad Sci 88:2788–2792
Song F, Stieger K (2017) Optimizing the DNA donor template for homology-directed repair of double-strand breaks. Mol Ther Nucleic Acids 7:53–60
Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62
Strecker J et al (2019) RNA-guided DNA insertion with CRISPR-associated transposases. Science 365:48–53. https://doi.org/10.1126/science.aax9181
Strocchio L, Locatelli F (2018) Hematopoietic stem cell transplantation in thalassemia. Hematol Oncol Clin North Am 32:317–328. https://doi.org/10.1016/j.hoc.2017.11.011
Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99:28–51. https://doi.org/10.1016/j.addr.2015.09.012
Taher AT, Weatherall DJ, Cappellini MD (2018) Thalassaemia. Lancet 391:155–167
Tebas P et al (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370:901–910. https://doi.org/10.1056/NEJMoa1300662
Teng F et al (2019) Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds. Genome Biol 20:15. https://doi.org/10.1186/s13059-019-1620-8
Thompson AA et al (2018) Gene therapy in patients with transfusion-dependent β-thalassemia. N Engl J Med 378:1479–1493
Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222
Till JE, McCulloch EA, Siminovitch L (1964) A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci 51:29–36
Tsai SQ et al (2015) GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33:187–197. https://doi.org/10.1038/nbt.3117
Tsai SQ et al (2017) CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets. Nat Methods 14:607–614. https://doi.org/10.1038/nmeth.4278
Uda M et al (2008) Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci U S A 105:1620–1625. https://doi.org/10.1073/pnas.0711566105
Verdera HC, Kuranda K, Mingozzi F (2020) AAV vector immunogenicity in humans: a long journey to successful gene transfer. Mol Ther 28:723–746. https://doi.org/10.1016/j.ymthe.2019.12.010
Vo PLH et al (2021) CRISPR RNA-guided integrases for high-efficiency, multiplexed bacterial genome engineering. Nat Biotechnol 39:480–489. https://doi.org/10.1038/s41587-020-00745-y
Wagner DL, Peter L, Schmueck-Henneresse M (2021) Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy? Gene Ther 28:549–559. https://doi.org/10.1038/s41434-021-00232-2
Walton RT, Christie KA, Whittaker MN, Kleinstiver BP (2020) Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants. Science 368:290–296. https://doi.org/10.1126/science.aba8853
Wright DA, Li T, Yang B, Spalding MH (2014) TALEN-mediated genome editing: prospects and perspectives. Biochem J 462:15–24
Wu A, Till J, Siminovitch L, McCulloch E (1967) A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells. J Cell Physiol 69:177–184
Wu AM, Till JE, Siminovitch L, McCulloch EA (1968) Cytological evidence for a relationship between normal hematopoietic colony-forming cells and cells of the lymphoid system. J Exp Med 127:455–464
Wu Y et al (2019) Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat Med 25:776–783. https://doi.org/10.1038/s41591-019-0401-y
Xu L et al (2019) CRISPR-edited stem cells in a patient with HIV and acute lymphocytic leukemia. N Engl J Med 381:1240–1247. https://doi.org/10.1056/NEJMoa1817426
Yang Y et al (2016) A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 34:334–338. https://doi.org/10.1038/nbt.3469
Yang H et al (2020) Methods favoring homology-directed repair choice in response to CRISPR/Cas9 induced-double strand breaks. Int J Mol Sci 21:6461
Yip BH (2020) Recent advances in CRISPR/Cas9 delivery strategies. Biomol Ther 10:839. https://doi.org/10.3390/biom10060839
Zeng J et al (2020) Therapeutic base editing of human hematopoietic stem cells. Nat Med 26:535–541. https://doi.org/10.1038/s41591-020-0790-y
Zetsche B et al (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759–771. https://doi.org/10.1016/j.cell.2015.09.038
Zhang F, Wen Y, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 23:R40–R46
Zhang W et al (2020a) A high-throughput small molecule screen identifies farrerol as a potentiator of CRISPR/Cas9-mediated genome editing. elife 9:e56008
Zhang X et al (2020b) Dual base editor catalyzes both cytosine and adenine base conversions in human cells. Nat Biotechnol 38:856–860. https://doi.org/10.1038/s41587-020-0527-y
Acknowledgments
This work was supported by the National Key R&D Program of China 2019YFA0110803 (Y.W.) and 2019YFA0109901 (Y.W.), grants from the Shanghai Municipal Commission for Science and Technology 19PJ1403500 (Y.W.), the National Science Foundation of China grants 32001061 (S.C.), and China Postdoctoral Science Foundation grants 2019M661430 (S.C.), 2019TQ0096 (S.C.), and 2020M681231 (J.L.).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Liao, J., Wu, Y. (2023). Gene Editing in Hematopoietic Stem Cells. In: Zhao, M., Qian, P. (eds) Hematopoietic Stem Cells. Advances in Experimental Medicine and Biology, vol 1442. Springer, Singapore. https://doi.org/10.1007/978-981-99-7471-9_11
Download citation
DOI: https://doi.org/10.1007/978-981-99-7471-9_11
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-7470-2
Online ISBN: 978-981-99-7471-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)