CRISPR-CAS9 as a tool for IT-15 gene editing in Huntington's Disease

Main Article Content

Letícia Alves de Godoy
https://orcid.org/0000-0002-4569-9260
Fernando Russo Costa do Bomfim
https://orcid.org/0000-0002-2614-3603

Abstract

Huntington's disease (HD) is a neurodegenerative, autosomal dominant and hereditary disease that occurs due to a genetic mutation that generates a repetitive sequence of CAG trinucleotides present in the IT-15 gene, huntingtin gene, located on chromosome 4. The objective was to review Huntington's disease (HD) neuropathology and the CRISPR-Cas9 method to silence the IT-15 gene and thus verify the consequence in the HIP14 and HAP1 genes, which have interaction with the mutated huntingtin and the result of this in the patient's organism. Articles were searched in indexed databases (Scielo, PubMed and LILACs) with the following descriptors: ((Huntington) OR (Huntingtin Protein)) AND (gene editing). The online tool GeneMania, open access, was also used to analyze probabilities and gene interactions. The silencing of the IT-15 gene causes changes in proteins that interact with the mutated Huntingtin, leading to disturbances in several processes.



Article Details

How to Cite
1.
Godoy LA de, Bomfim FRC do. CRISPR-CAS9 as a tool for IT-15 gene editing in Huntington’s Disease. HSJ [Internet]. 2020 Dec. 2 [cited 2024 Nov. 22];10(4):10-5. Available from: https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/1016
Section
NARRATIVE REVIEW
Author Biographies

Letícia Alves de Godoy, Molecular Biology Laboratory, University Center of the Hermínio Ometto Foundation (FHO)

Student of the Bachelor's Degree in Biomedicine at University Center of the Hermínio Ometto Foundation (FHO). Araras, São Paulo, Brazil.

Fernando Russo Costa do Bomfim, University Center of the Hermínio Ometto Foundation (FHO)

PhD, Professor of Molecular Biology at the University Center of Fundação Hermínio Ometto (FHO), Araras, São Paulo, Brazil. Postdoctoral fellow at the Federal University of São Paulo / EPM. São Paulo, São Paulo, Brazil.

References

van der Burg JM, Björkqvist M, Brundin P. Beyond the brain: widespread pathology in Huntington's disease. Lancet Neurol. 2009;8(8):765-74. https://doi.org/10.1016/S1474-4422(09)70178-4

Martelli A. Aspectos clínicos e fisiopatológicos da doença de Huntington. Arch Health Invest [Internet]. 2014 [cited 2020 22 Sep];3(4):32-39. Avaiable from: http://www.archhealthinvestigation.com.br/ArcHI/article/view/687

Gil-Mohapel JM, Rego AC. Doença de Huntington: uma revisão dos aspectos fisiopatológicos. Rev Neurocienc 2011;19(4):724-34. https://doi.org/10.34024/rnc.2011.v19.8332

Shannon KM. Recent Advances in the Treatment of Huntington's Disease: Targeting DNA and RNA. CNS Drugs. 2020;34(3):219-228. https://doi.org/10.1007/s40263-019-00695-3 PMid:31933283

Intrieri ACU, Filho HB, Sabino MRLS, Ismail M, Furtado CC. Huntington: distúrbio no cromossomo 4. Rev UNILUS Ens Pesq [Internet]. 2015 [cited 2020 Sep 22];12(29):22-34. Avaiable from: http://revista.lusiada.br/index.php/ruep/article/view/687

Kaltenbach LS, Romero E, Becklin RR, et al. Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet. 2007;3(5):e82. https://doi.org/10.1371/journal.pgen.0030082 PMid:17500595 PMCid:PMC1866352

Kolli N, Lu M, Maiti P, Rossignol J, Dunbar GL. CRISPR-Cas9 Mediated Gene-Silencing of the Mutant Huntingtin Gene in an In Vitro Model of Huntington's Disease. Int J Mol Sci. 2017;18(4):754. https://doi.org/10.3390/ijms18040754 PMid:28368337 PMCid:PMC5412339

Gonçalves GAR, Paiva RMA. Terapia gênica: avanços, desafios e perspectivas. Einstein (São Paulo) [Internet]. 2017;15(3):369-75. https://doi.org/10.1590/s1679-45082017rb4024 PMid:29091160 PMCid:PMC5823056

Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010; 38(Suppl 2):W214-20. https://doi.org/10.1093/nar/gkq537 PMid:20576703 PMCid:PMC2896186

Saudou F, Humbert S. The biology of Huntingtin. Neuron. 2016;89(5):910-26. https://doi.org/10.1016/j.neuron.2016.02.003 PMid:26938440

ABH: Associação Brasil Huntington [Internet site]. Contexto genético da DH [access 2020 Nov 12]. Avaiable from: http://abh.org.br/o-que-e-doenca-de-huntington/contexto-genetico-da-dh/

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993;72(6):971-83. https://doi.org/10.1016/0092-8674(93)90585-E

Gusella JA, MacDonald ME. Huntington's Disease: seeing the pathogenic process through a genetic lens. Trends Biochem Sci. 2006;31(9):533-40. https://doi.org/10.1186/gm80 PMid:19725930 PMCid:PMC2768966

Landles C, Bates GP. Huntingtin and the molecular pathogenesis of Huntington's Disease. EMBO Rep. 2004;5:958-63. https://doi.org/10.1038/sj.embor.7400250 PMid:15459747 PMCid:PMC1299150

Spitz M. Doença de Huntington e outras coréias. Rev Hosp Universitário Pedro Ernesto. 2010;9(1):29-38.

Frank S. Tetrabenazine: the first approved drug for the treatment of chorea in US patients with Huntington disease. Neuropsychiatric disease and treatment. 2010;6(1):657-65. https://doi.org/10.2147/NDT.S6430 PMid:20957126 PMCid:PMC2951749

Nance MA. Therapy in Huntington's Disease: where are we? Curr Neurol Neurosci Rep. 2012;12(4):359-66. https://doi.org/10.1007/s11910-012-0277-4 PMid:22544535

Shin JW, Kim KH, Chao MJ, et al. Permanent inactivation of Huntington's disease mutation by personalized allele-specific CRISPR/Cas9. Human Molecular Genetics. 2016;25(20):4566-76. https://doi.org/10.1093/hmg/ddw286 PMid:28172889 PMCid:PMC6078600

Ravache M, Abou-Sleymane G, Trottier Y. Neurodegenerative polyglutamine expansion diseases: physiopathology and therapeutic strategies. Pathol Biol (Paris). 2010;58(5):357-66. https://doi.org/10.1016/j.patbio.2009.12.004 PMid:20299163

Sun Y, Savanenin A, Reddy PH, Liu YF. Polyglutamine-expanded huntingtin promotes sensitization of n-methyl-d-aspartate receptors via post-synaptic density 95. J Biol Chem. 2001;276(27):24713-8. https://doi.org/10.1074/jbc.M103501200 PMid:11319238

Li XJ, Li SH, Sharp AH, et al. Huntingtin-associated protein enriched in brain with implications for pathology. Nature. 1995;378(6555):398-402. https://doi.org/10.1038/378398a0 PMid:7477378

Arend MC, Pereira JO, Markorski MM. O Sistema CRISPR/Cas9 e a possibilidade de edição genômica para a cardiologia. Arq Bras Cardiol. 2017;108(1):81-3. https://dx.doi.org/10.5935/abc.20160200

Yang W, Tu Z, Sun Q, Li XJ. CRISPR/Cas9: Implications for modeling and therapy of neurodegenerative diseases. Front Mol Neurosci. 2016;9(30):1-4. https://doi.org/10.3389/fnmol.2016.00030

Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J. RNA-programmed genome editing in human cells. eLife. 2013;2:e00471. https://doi.org/10.7554/eLife.00471 PMid:23386978 PMCid:PMC3557905

Savic N, Schwank G. Advances in therapeutic CRISPR/Cas9 genome editing. Transl Res. 2016;168:15-21. https://doi.org/10.1016/j.trsl.2015.09.008 PMid:26470680

Singaraja RR, Huang K, Sanders SS, et al. Altered palmitoylation and neuropathological deficits in mice lacking HIP14. Hum Mol Genet. 2011;20(20):3899-909. https://doi.org/10.1093/hmg/ddr308 PMid:21775500 PMCid:PMC3177655