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2000
Volume 26, Issue 10
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Motor neuron disorders encompass a spectrum of conditions that can be inherited or arise from spontaneous gene mutations. These disorders disrupt the crucial connection between motor neurons and muscles, leading to a range of symptoms, including muscle weakness, impaired coordination, and abnormal movements. Unfortunately, despite the significant impact on individuals' quality of life, there is currently no definitive cure for these disorders.

In response to this pressing medical need, extensive research efforts are underway globally to develop effective treatments for motor neuron disorders. Among the emerging therapeutic strategies, gene therapy has shown considerable promise. By targeting the underlying genetic abnormalities responsible for these disorders, gene therapy aims to correct or mitigate the dysfunctional molecular pathways, offering hope for improved outcomes and potentially even disease reversal. Various approaches are being explored within the realm of gene therapy, with genetic modification techniques taking center stage. These techniques enable precise manipulation of the genetic material, facilitating the replacement of mutated genes with functional ones. One such technique that has garnered attention for its potential therapeutic efficacy is Zinc Finger Nucleases (ZFNs). ZFNs are molecular tools designed to target specific DNA sequences with high precision, enabling targeted gene editing. Their ability to induce targeted modifications in the genome holds significant promise for treating motor neuron disorders by correcting disease-causing mutations. Moreover, ZFNs offer advantages such as accuracy and desirable therapeutic effects, making them an attractive option for gene therapy applications. Despite their potential, it is essential to acknowledge the limitations and challenges associated with ZFN-based gene therapy. These include off-target effects, delivery methods, and immune responses. Understanding and addressing these challenges are critical steps toward realizing the full therapeutic potential of ZFNs in treating motor neuron disorders. In this comprehensive review, we delve into the intricacies of ZFNs, exploring their mechanisms of action, current applications, limitations, and future prospects in gene therapy for motor neuron disorders. Additionally, we provide insights into other nucleases-mediated gene therapy approaches, highlighting their comparative advantages and challenges. Furthermore, we discuss factors influencing the efficacy and safety of gene therapy treatments, including delivery methods, immune responses, and ethical considerations. By examining these factors in detail, we aim to provide a holistic understanding of the complex landscape of gene therapy for motor neuron disorders and pave the way for future advancements in the field.

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References

  1. TiryakiE. HorakH.A. ALS and other motor neuron diseases.Continuum (Minneap. Minn.)2014205 Peripheral Nervous System Disorders1185120710.1212/01.CON.0000455886.14298.a4 25299277
     [Google Scholar]
  2. TalbotK. Motor neuron disease: The bare essentials.Pract. Neurol.20099530330910.1136/jnnp.2009.188151 19762894
     [Google Scholar]
  3. VerberN.S. ShepheardS.R. SassaniM. McDonoughH.E. MooreS.A. AlixJ.J.P. WilkinsonI.D. JenkinsT.M. ShawP.J. Biomarkers in motor neuron disease: A state of the art review.Front. Neurol.20191029110.3389/fneur.2019.00291 31001186
     [Google Scholar]
  4. MiccioA. AntoniouP. CiuraS. KabashiE. Novel genome-editing-based approaches to treat motor neuron diseases: Promises and challenges.Mol. Ther.2022301475310.1016/j.ymthe.2021.04.003 33823304
     [Google Scholar]
  5. UrnovF.D. RebarE.J. HolmesM.C. ZhangH.S. GregoryP.D. Genome editing with engineered zinc finger nucleases.Nat. Rev. Genet.201011963664610.1038/nrg2842 20717154
     [Google Scholar]
  6. TalbotK. Motor neurone disease.Postgrad. Med. J.20027892351351910.1136/pmj.78.923.513 12357010
     [Google Scholar]
  7. DharmadasaT. HendersonR.D. TalmanP.S. MacdonellR.A.L. MathersS. SchultzD.W. NeedhamM. ZoingM. VucicS. KiernanM.C. Motor neurone disease: Progress and challenges.Med. J. Aust.2017206835736210.5694/mja16.01063 28446118
     [Google Scholar]
  8. FeldmanE.L. GoutmanS.A. PetriS. MazziniL. SavelieffM.G. ShawP.J. SobueG. Amyotrophic lateral sclerosis.Lancet2022400103601363138010.1016/S0140‑6736(22)01272‑7 36116464
     [Google Scholar]
  9. BrownR.H. Al-ChalabiA. Amyotrophic lateral sclerosis.N. Engl. J. Med.2017377216217210.1056/NEJMra1603471 28700839
     [Google Scholar]
  10. HardimanO. van den BergL.H. KiernanM.C. Clinical diagnosis and management of amyotrophic lateral sclerosis.Nat. Rev. Neurol.201171163964910.1038/nrneurol.2011.153 21989247
     [Google Scholar]
  11. KaramC. ScelsaS.N. MacGowanD.J.L. The clinical course of progressive bulbar palsy.Amyotroph. Lateral Scler.201011436436810.3109/17482960903513159 20132084
     [Google Scholar]
  12. ZhangH.G. ChenL. TangL. ZhangN. FanD.S. Clinical features of isolated bulbar palsy of amyotrophic lateral sclerosis in Chinese population.Chin. Med. J. (Engl.)2017130151768177210.4103/0366‑6999.211538 28748847
     [Google Scholar]
  13. StatlandJ.M. BarohnR.J. DimachkieM.M. FloeterM.K. MitsumotoH. Primary lateral sclerosis.Neurol. Clin.201533474976010.1016/j.ncl.2015.07.007 26515619
     [Google Scholar]
  14. TurnerM.R. BarohnR.J. CorciaP. FinkJ.K. HarmsM.B. KiernanM.C. RavitsJ. SilaniV. SimmonsZ. StatlandJ. van den BergL.H. MitsumotoH. Primary lateral sclerosis: Consensus diagnostic criteria.J. Neurol. Neurosurg. Psychiatry202091437337710.1136/jnnp‑2019‑322541 32029539
     [Google Scholar]
  15. WaisV. RosenbohmA. PetriS. KolleweK. HermannA. StorchA. HanischF. ZierzS. NagelG. KassubekJ. WeydtP. BrettschneiderJ. WeishauptJ.H. LudolphA.C. DorstJ. The concept and diagnostic criteria of primary lateral sclerosis.Acta Neurol. Scand.2017136320421110.1111/ane.12713 27858953
     [Google Scholar]
  16. LiewluckT. SapersteinD.S. Progressive muscular atrophy.Neurol. Clin.201533476177310.1016/j.ncl.2015.07.005 26515620
     [Google Scholar]
  17. KimW.K. LiuX. SandnerJ. PasmantierM. AndrewsJ. RowlandL.P. MitsumotoH. Study of 962 patients indicates progressive muscular atrophy is a form of ALS.Neurology200973201686169210.1212/WNL.0b013e3181c1dea3 19917992
     [Google Scholar]
  18. MercuriE. PeraM.C. ScotoM. FinkelR. MuntoniF. Spinal muscular atrophy — insights and challenges in the treatment era.Nat. Rev. Neurol.2020161270671510.1038/s41582‑020‑00413‑4 33057172
     [Google Scholar]
  19. LunnM.R. WangC.H. Spinal muscular atrophy.Lancet200837196302120213310.1016/S0140‑6736(08)60921‑6 18572081
     [Google Scholar]
  20. PriorT.W. LeachM.E. FinangerE. Spinal muscular atrophy.Seattle, (WA)University of Washington199319932024
     [Google Scholar]
  21. BrezaM. KoutsisG. Kennedy’s disease (spinal and bulbar muscular atrophy): A clinically oriented review of a rare disease.J. Neurol.2019266356557310.1007/s00415‑018‑8968‑7 30006721
     [Google Scholar]
  22. ArnoldF.J. MerryD.E. Molecular mechanisms and therapeutics for SBMA/Kennedy’s disease.Neurotherapeutics201916492894710.1007/s13311‑019‑00790‑9 31686397
     [Google Scholar]
  23. ChenJ. LongX. HanY. Using genetic testing to diagnose Kennedy’s disease: A case report and literature review.Am. J. Transl. Res.202113674127417 34306514
     [Google Scholar]
  24. OlunuE. FakoyaA.O. OluwasanmiO.J. MckenzieD.A. AdewoleI.O. AlukaC.O. IyasseJ. Postpolio syndrome: A review of lived experiences of patients.Int. J. Appl. Basic Med. Res.20199312913410.4103/ijabmr.IJABMR_333_18 31392174
     [Google Scholar]
  25. JubeltB. Post-polio syndrome.Curr. Treat. Options Neurol.200462879310.1007/s11940‑004‑0018‑3 14759341
     [Google Scholar]
  26. FarbuE. GilhusN.E. BarnesM.P. BorgK. De VisserM. DriessenA. HowardR. NolletF. OparaJ. StalbergE. EFNS guideline on diagnosis and management of post‐polio syndrome. Report of an EFNS task force.Eur. J. Neurol.200613879580110.1111/j.1468‑1331.2006.01385.x 16879288
     [Google Scholar]
  27. KhalilA.M. The genome editing revolution: Review.J. Genet. Eng. Biotechnol.20201816810.1186/s43141‑020‑00078‑y 33123803
     [Google Scholar]
  28. DoudnaJ.A. The promise and challenge of therapeutic genome editing.Nature2020578779422923610.1038/s41586‑020‑1978‑5 32051598
     [Google Scholar]
  29. GajT. SirkS.J. ShuiS. LiuJ. Genome-editing technologies: Principles and applications.Cold Spring Harb. Perspect. Biol.2016812a02375410.1101/cshperspect.a023754 27908936
     [Google Scholar]
  30. ChaytowH. FallerK.M.E. HuangY.T. GillingwaterT.H. Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell Rep. Med.20212710034610.1016/j.xcrm.2021.100346 34337562
     [Google Scholar]
  31. RaoVK KappD SchrothM Gene therapy for spinal muscular atrophy: An emerging treatment option for a devastating disease.J Manag Care Spec Pharm20182412-a SupplS3S1610.18553/jmcp.2018.24.12‑a.s3
     [Google Scholar]
  32. IftikharM. FreyJ. ShohanM.J. MalekS. MousaS.A. Current and emerging therapies for Duchenne muscular dystrophy and spinal muscular atrophy.Pharmacol. Ther.202122010771910.1016/j.pharmthera.2020.107719 33130193
     [Google Scholar]
  33. MessinaS. SframeliM. New treatments in spinal muscular atrophy: Positive results and new challenges.J. Clin. Med.202097222210.3390/jcm9072222 32668756
     [Google Scholar]
  34. PeregoM.G.L. GalliN. NizzardoM. GovoniA. TaianaM. BresolinN. ComiG.P. CortiS. Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).Cell. Mol. Life Sci.202077173351336710.1007/s00018‑020‑03492‑0 32123965
     [Google Scholar]
  35. KarpeY. ChenZ. LiX.J. Stem cell models and gene targeting for human motor neuron diseases.Pharmaceuticals202114656510.3390/ph14060565 34204831
     [Google Scholar]
  36. MikkelsenN.S. BakR.O. Enrichment strategies to enhance genome editing.J. Biomed. Sci.20233015110.1186/s12929‑023‑00943‑1 37393268
     [Google Scholar]
  37. BibikovaM. BeumerK. TrautmanJ.K. CarrollD. Enhancing gene targeting with designed zinc finger nucleases.Science2003300562076410.1126/science.1079512 12730594
     [Google Scholar]
  38. ManiM. KandavelouK. DyF.J. DuraiS. ChandrasegaranS. Design, engineering, and characterization of zinc finger nucleases.Biochem. Biophys. Res. Commun.2005335244745710.1016/j.bbrc.2005.07.089 16084494
     [Google Scholar]
  39. CarrollD. Genome engineering with zinc-finger nucleases.Genetics2011188477378210.1534/genetics.111.131433 21828278
     [Google Scholar]
  40. MarintchevaB. Harnessing the power of viruses.Academic Press2017
     [Google Scholar]
  41. RedmanM. KingA. WatsonC. KingD. What is CRISPR/Cas9?Arch. Dis. Child. Educ. Pract. Ed.2016101421321510.1136/archdischild‑2016‑310459 27059283
     [Google Scholar]
  42. MoonS.B. KimD.Y. KoJ.H. KimY.S. Recent advances in the CRISPR genome editing tool set.Exp. Mol. Med.2019511111110.1038/s12276‑019‑0339‑7 31685795
     [Google Scholar]
  43. NemudryiA.A. ValetdinovaK.R. MedvedevS.P. ZakianS.M. TALEN and CRISPR/Cas genome editing systems: Tools of discovery.Acta Nat. (Engl. Ed.)201463194010.32607/20758251‑2014‑6‑3‑19‑40 25349712
     [Google Scholar]
  44. RazaS.H.A. HassaninA.A. PantS.D. BingS. SitohyM.Z. AbdelnourS.A. AlotaibiM.A. Al-HazaniT.M. Abd El-AzizA.H. ChengG. ZanL. Potentials, prospects and applications of genome editing technologies in livestock production.Saudi J. Biol. Sci.20222941928193510.1016/j.sjbs.2021.11.037 35531207
     [Google Scholar]
  45. BordbarM. DarvishzadehR. PazhouhandehM. KahriziD. An overview of genome editing methods based on endonucleases.Scientific Quarterly Journal of Modern Genetics20201527592
     [Google Scholar]
  46. GalettoR. DuchateauP. PâquesF. Targeted approaches for gene therapy and the emergence of engineered meganucleases.Expert Opin. Biol. Ther.20099101289130310.1517/14712590903213669 19689185
     [Google Scholar]
  47. KhanS.H. Genome-editing technologies: Concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application.Mol. Ther. Nucleic Acids20191632633410.1016/j.omtn.2019.02.027 30965277
     [Google Scholar]
  48. DavisD. StokoeD. Zinc Finger Nucleases as tools to understand and treat human diseases.BMC Med.2010814210.1186/1741‑7015‑8‑42 20594338
     [Google Scholar]
  49. HändelE.M. CathomenT. Zinc-finger nuclease based genome surgery: It’s all about specificity.Curr. Gene Ther.2011111283710.2174/156652311794520120 21182467
     [Google Scholar]
  50. AinQ.U. ChungJ.Y. KimY.H. Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN.J. Control. Release201520512012710.1016/j.jconrel.2014.12.036 25553825
     [Google Scholar]
  51. LiX. HanM. ZhangH. LiuF. PanY. ZhuJ. LiaoZ. ChenX. ZhangB. Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma.Biomark. Res.2022101210.1186/s40364‑021‑00345‑1 35000617
     [Google Scholar]
  52. KlugA. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation.Q. Rev. Biophys.201043112110.1017/S0033583510000089 20478078
     [Google Scholar]
  53. HalfordS.E. CattoL.E. PernstichC. RuslingD.A. SandersK.L. The reaction mechanism of FokI excludes the possibility of targeting zinc finger nucleases to unique DNA sites.Biochem. Soc. Trans.201139258458810.1042/BST0390584 21428944
     [Google Scholar]
  54. MillerJ.C. HolmesM. WangJ. LeeY.L. RupniewskiI. WaiteA. GuschinD. GregoryP. PaboC.O. RebarE.J. 787. Engineered Fok I Heterodimers for Enhanced Zinc Finger Nuclease Specificity.Mol. Ther.200613S30510.1016/j.ymthe.2006.08.875
     [Google Scholar]
  55. HarmatzP. PradaC.E. BurtonB.K. LauH. KesslerC.M. CaoL. FalaleevaM. VillegasA.G. ZeitlerJ. MeyerK. MillerW. Wong Po FooC. VaidyaS. SwensonW. ShiueL.H. RouyD. MuenzerJ. First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.Mol. Ther.202230123587360010.1016/j.ymthe.2022.10.010 36299240
     [Google Scholar]
  56. HändelE.M. AlwinS. CathomenT. Expanding or restricting the target site repertoire of zinc-finger nucleases: The inter-domain linker as a major determinant of target site selectivity.Mol. Ther.200917110411110.1038/mt.2008.233 19002164
     [Google Scholar]
  57. BibikovaM. GolicM. GolicK.G. CarrollD. Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases.Genetics200216131169117510.1093/genetics/161.3.1169 12136019
     [Google Scholar]
  58. WaryahCB MosesC AroojM BlancafortP Zinc fingers, TALEs, and CRISPR systems: A comparison of tools for epigenome editing.Epigenome editing: methods and protocols20181963
     [Google Scholar]
  59. CaiY. BakR.O. MikkelsenJ.G. Targeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases.eLife20143e0191110.7554/eLife.01911 24843011
     [Google Scholar]
  60. Perez-PineraP. OusteroutD.G. BrownM.T. GersbachC.A. Gene targeting to the ROSA26 locus directed by engineered zinc finger nucleases.Nucleic Acids Res.20124083741375210.1093/nar/gkr1214 22169954
     [Google Scholar]
  61. ZhangH.X. ZhangY. YinH. Genome editing with mRNA encoding ZFN, TALEN, and Cas9.Mol. Ther.201927473574610.1016/j.ymthe.2019.01.014 30803822
     [Google Scholar]
  62. KimY.G. ChaJ. ChandrasegaranS. Hybrid restriction enzymes: Zinc finger fusions to Fok I cleavage domain.Proc. Natl. Acad. Sci. USA19969331156116010.1073/pnas.93.3.1156 8577732
     [Google Scholar]
  63. CarrollD. Genome engineering with targetable nucleases.Annu. Rev. Biochem.201483140943910.1146/annurev‑biochem‑060713‑035418 24606144
     [Google Scholar]
  64. NaeemM. MajeedS. HoqueM.Z. AhmadI. Latest developed strategies to minimize the off-target effects in CRISPR-Cas-mediated genome editing.Cells202097160810.3390/cells9071608 32630835
     [Google Scholar]
  65. LejmanJ. PanuciakK. NowickaE. MastalerczykA. WojciechowskaK. LejmanM. Gene therapy in ALS and SMA: Advances, challenges and perspectives.Int. J. Mol. Sci.2023242113010.3390/ijms24021130 36674643
     [Google Scholar]
  66. ZhangP.W. Haidet-PhillipsA.M. PhamJ.T. LeeY. HuoY. TienariP.J. MaragakisN.J. SattlerR. RothsteinJ.D. Generation of GFAP:GFP astrocyte reporter lines from human adult fibroblast‐derived i PS cells using zinc‐finger nuclease technology.Glia2016641637510.1002/glia.22903 26295203
     [Google Scholar]
  67. YinH. KauffmanK.J. AndersonD.G. Delivery technologies for genome editing.Nat. Rev. Drug Discov.201716638739910.1038/nrd.2016.280 28337020
     [Google Scholar]
  68. WangL. LiF. DangL. LiangC. WangC. HeB. LiuJ. LiD. WuX. XuX. LuA. ZhangG. In vivo delivery systems for therapeutic genome editing.Int. J. Mol. Sci.201617562610.3390/ijms17050626 27128905
     [Google Scholar]
  69. NayerossadatN. MaedehT. AliP. Viral and nonviral delivery systems for gene delivery.Adv. Biomed. Res.2012112710.4103/2277‑9175.98152 23210086
     [Google Scholar]
  70. MaggioI. ZittersteijnH.A. WangQ. LiuJ. JanssenJ.M. OjedaI.T. van der MaarelS.M. LankesterA.C. HoebenR.C. GonçalvesM.A.F.V. Integrating gene delivery and gene-editing technologies by adenoviral vector transfer of optimized CRISPR-Cas9 components.Gene Ther.202027520922510.1038/s41434‑019‑0119‑y 31900423
     [Google Scholar]
  71. SiosonV.A. KimM. JooJ. Challenges in delivery systems for CRISPR-based genome editing and opportunities of nanomedicine.Biomed. Eng. Lett.202111321723310.1007/s13534‑021‑00199‑4 34350049
     [Google Scholar]
  72. WilbieD. WaltherJ. MastrobattistaE. Delivery aspects of CRISPR/Cas for in vivo genome editing.Acc. Chem. Res.20195261555156410.1021/acs.accounts.9b00106 31099553
     [Google Scholar]
  73. SungY.K. KimS.W. Recent advances in the development of gene delivery systems.Biomater. Res.2019231810.1186/s40824‑019‑0156‑z 30915230
     [Google Scholar]
  74. BrooksI.R. SheriffA. MoranD. WangJ. JackówJ. Challenges of gene editing therapies for genodermatoses.Int. J. Mol. Sci.2023243229810.3390/ijms24032298 36768619
     [Google Scholar]
  75. LiuW. LiL. JiangJ. WuM. LinP. Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics.Precis. Clin. Med.20214317919110.1093/pcmedi/pbab014 34541453
     [Google Scholar]
  76. PavlovicK. Tristán-ManzanoM. Maldonado-PérezN. Cortijo-GutierrezM. Sánchez-HernándezS. Justicia-LirioP. CarmonaM.D. HerreraC. MartinF. BenabdellahK. Using gene editing approaches to fine-tune the immune system.Front. Immunol.20201157067210.3389/fimmu.2020.570672 33117361
     [Google Scholar]
  77. PetraitytėG. PreikšaitienėE. MikštienėV. Genome editing in medicine: Tools and challenges.Acta Med. Litu.2021282810.15388/Amed.2021.28.2.8 35637939
     [Google Scholar]
  78. CamenischT. BrilliantM. SegalD. Critical parameters for genome editing using zinc finger nucleases.Mini Rev. Med. Chem.20088766967610.2174/138955708784567458 18537722
     [Google Scholar]
  79. LiH. YangY. HongW. HuangM. WuM. ZhaoX. Applications of genome editing technology in the targeted therapy of human diseases: Mechanisms, advances and prospects.Signal Transduct. Target. Ther.202051110.1038/s41392‑019‑0089‑y 32296011
     [Google Scholar]
  80. HuttanusH.M. TriolaE.K.H. Velasquez-GuzmanJ.C. ShinS.M. Granja-TravezR.S. SinghA. DaleT. JhaR.K. Targeted mutagenesis and high-throughput screening of diversified gene and promoter libraries for isolating gain-of-function mutations.Front. Bioeng. Biotechnol.202311120238810.3389/fbioe.2023.1202388 37545889
     [Google Scholar]
  81. HumbertO. DavisL. MaizelsN. Targeted gene therapies: Tools, applications, optimization.Crit. Rev. Biochem. Mol. Biol.201247326428110.3109/10409238.2012.658112 22530743
     [Google Scholar]
  82. De RavinS.S. ReikA. LiuP.Q. LiL. WuX. SuL. RaleyC. TheobaldN. ChoiU. SongA.H. ChanA. PearlJ.R. PaschonD.E. LeeJ. NewcombeH. KoontzS. SweeneyC. ShivakD.A. ZaremberK.A. PeshwaM.V. GregoryP.D. UrnovF.D. MalechH.L. Targeted gene addition in human CD34+ hematopoietic cells for correction of X-linked chronic granulomatous disease.Nat. Biotechnol.201634442442910.1038/nbt.3513 26950749
     [Google Scholar]
  83. Pruett-MillerS.M. ReadingD.W. PorterS.N. PorteusM.H. Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels.PLoS Genet.200952e100037610.1371/journal.pgen.1000376 19214211
     [Google Scholar]
  84. ChouS.T. LengQ. MixsonJ. Zinc finger nucleases: Tailor-made for gene therapy.Drugs Future201237318319610.1358/dof.2012.37.3.1779022 24155503
     [Google Scholar]
  85. CornuT.I. Thibodeau-BegannyS. GuhlE. AlwinS. EichtingerM. JoungJ.K. CathomenT. DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases.Mol. Ther.200816235235810.1038/sj.mt.6300357
     [Google Scholar]
  86. KohnD.B. PorteusM.H. ScharenbergA.M. Ethical and regulatory aspects of genome editing.Blood2016127212553256010.1182/blood‑2016‑01‑678136 27053531
     [Google Scholar]
  87. HendelA. FineE.J. BaoG. PorteusM.H. Quantifying on- and off-target genome editing.Trends Biotechnol.201533213214010.1016/j.tibtech.2014.12.001 25595557
     [Google Scholar]
  88. HajiahmadiZ. MovahediA. WeiH. LiD. OroojiY. RuanH. ZhugeQ. Strategies to increase on-target and reduce off-target effects of the CRISPR/Cas9 system in plants.Int. J. Mol. Sci.20192015371910.3390/ijms20153719 31366028
     [Google Scholar]
  89. MillerJ.C. HolmesM.C. WangJ. GuschinD.Y. LeeY.L. RupniewskiI. BeausejourC.M. WaiteA.J. WangN.S. KimK.A. GregoryP.D. PaboC.O. RebarE.J. An improved zinc-finger nuclease architecture for highly specific genome editing.Nat. Biotechnol.200725777878510.1038/nbt1319 17603475
     [Google Scholar]
  90. PorteusM.H. CarrollD. Gene targeting using zinc finger nucleases.Nat. Biotechnol.200523896797310.1038/nbt1125 16082368
     [Google Scholar]
  91. LopesR. PrasadM.K. Beyond the promise: Evaluating and mitigating off-target effects in CRISPR gene editing for safer therapeutics.Front. Bioeng. Biotechnol.202411133918910.3389/fbioe.2023.1339189 38390600
     [Google Scholar]
  92. KadamU.S. ShelakeR.M. ChavhanR.L. SuprasannaP. Concerns regarding ‘off-target’ activity of genome editing endonucleases.Plant Physiol. Biochem.2018131223010.1016/j.plaphy.2018.03.027 29653762
     [Google Scholar]
  93. PattanayakV. RamirezC.L. JoungJ.K. LiuD.R. Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection.Nat. Methods20118976577010.1038/nmeth.1670 21822273
     [Google Scholar]
  94. KovalchukI. Off-target effects in genome editing.Genome Stability20212671572710.1016/B978‑0‑323‑85679‑9.00038‑6
     [Google Scholar]
  95. Ashmore-HarrisC. FruhwirthG.O. The clinical potential of gene editing as a tool to engineer cell‐based therapeutics.Clin. Transl. Med.202091e1510.1186/s40169‑020‑0268‑z 32034584
     [Google Scholar]
  96. MarchantG.E. Global governance of human genome editing: What are the rules?Annu. Rev. Genomics Hum. Genet.202122138540510.1146/annurev‑genom‑111320‑091930 33667117
     [Google Scholar]
  97. RanY. PatronN. KayP. WongD. BuchananM. CaoY.Y. SawbridgeT. DaviesJ.P. MasonJ. WebbS.R. SpangenbergG. AinleyW.M. WalshT.A. HaydenM.J. Zinc finger nuclease‐mediated precision genome editing of an endogenous gene in hexaploid bread wheat (Triticum aestivum) using a DNA repair template.Plant Biotechnol. J.201816122088210110.1111/pbi.12941 29734518
     [Google Scholar]
  98. StraimerJ. LeeM.C.S. LeeA.H. ZeitlerB. WilliamsA.E. PearlJ.R. ZhangL. RebarE.J. GregoryP.D. LlinásM. UrnovF.D. FidockD.A. Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleases.Nat. Methods201291099399810.1038/nmeth.2143 22922501
     [Google Scholar]
  99. PauwelsK. PodevinN. BreyerD. CarrollD. HermanP. Engineering nucleases for gene targeting: Safety and regulatory considerations.N. Biotechnol.2014311182710.1016/j.nbt.2013.07.001 23851284
     [Google Scholar]
  100. CarrollD. Progress and prospects: Zinc-finger nucleases as gene therapy agents.Gene Ther.200815221463146810.1038/gt.2008.145 18784746
     [Google Scholar]
  101. QiuR. Debating ethical issues in genome editing technology.Asian Bioeth. Rev.20168430732610.1353/asb.2016.0026
     [Google Scholar]
  102. KaragyaurMN EfimenkoAYu MakarevichPI VasiluePA AkopyanZhA BryzgalinaE.V TkachukVA. Ethical and legal issues in the use of genome editing technologies in medicine (review).Modern technologies in medicine2019113117135
     [Google Scholar]
  103. AyanoğluF.B. Elçi̇nA.E. Elçi̇nY.M. Bioethical issues in genome editing by CRISPR-Cas9 technology.Turk. J. Biol.202044211012010.3906/biy‑1912‑52 32256147
     [Google Scholar]
  104. CoxD.B.T. PlattR.J. ZhangF. Therapeutic genome editing: Prospects and challenges.Nat. Med.201521212113110.1038/nm.3793 25654603
     [Google Scholar]
  105. SelinC. LambertL. MorainS. NelsonJ.P. BarlevyD. FarooqueM. ManleyH. ScottC.T. Researching the future: Scenarios to explore the future of human genome editing.BMC Med. Ethics20232417210.1186/s12910‑023‑00951‑8 37735670
     [Google Scholar]
  106. AmerM.H. Gene therapy for cancer: Present status and future perspective.Mol. Cell. Ther.2014212710.1186/2052‑8426‑2‑27 26056594
     [Google Scholar]
  107. LongC. AmoasiiL. Bassel-DubyR. OlsonE.N. Genome editing of monogenic neuromuscular diseases: A systematic review.JAMA Neurol.201673111349135510.1001/jamaneurol.2016.3388 27668807
     [Google Scholar]
  108. GuptaA. MengX. ZhuL.J. LawsonN.D. WolfeS.A. Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases.Nucleic Acids Res.201139138139210.1093/nar/gkq787 20843781
     [Google Scholar]
  109. LiuJ. ShuiS. Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.J. Control. Release2016244Pt A839710.1016/j.jconrel.2016.11.014 27865852
     [Google Scholar]
  110. PalpantN.J. DudzinskiD. Zinc finger nucleases: Looking toward translation.Gene Ther.201320212112710.1038/gt.2012.2 22318089
     [Google Scholar]
  111. WangY. ZhangW.Y. HuS. LanF. LeeA.S. HuberB. LisowskiL. LiangP. HuangM. de AlmeidaP.E. WonJ.H. SunN. RobbinsR.C. KayM.A. UrnovF.D. WuJ.C. Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging.Circ. Res.2012111121494150310.1161/CIRCRESAHA.112.274969 22967807
     [Google Scholar]
  112. UrnovF.D. MillerJ.C. LeeY.L. BeausejourC.M. RockJ.M. AugustusS. JamiesonA.C. PorteusM.H. GregoryP.D. HolmesM.C. Highly efficient endogenous human gene correction using designed zinc-finger nucleases.Nature2005435704264665110.1038/nature03556 15806097
     [Google Scholar]
  113. GersbachC.A. GajT. BarbasC.F. III Synthetic zinc finger proteins: The advent of targeted gene regulation and genome modification technologies.Acc. Chem. Res.20144782309231810.1021/ar500039w 24877793
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010307288240526071810
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Genome Editing Approaches Using Zinc Finger Nucleases (ZFNs) for the Treatment of Motor Neuron Diseases
Current Pharmaceutical Biotechnology 26, 1514 (2025); https://doi.org/10.2174/0113892010307288240526071810
/content/journals/cpb/10.2174/0113892010307288240526071810
/content/journals/cpb/10.2174/0113892010307288240526071810
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  • Article Type:     Review Article
Keyword(s): FOK I catalytic domain; gene delivery systems; gene therapy; genome editing techniques; motor neuron disorders; Zinc finger nucleases

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