ENGENHARIA GENÉTICA, CRISPR E DOENÇAS CARDIOVASCULARES: A EDIÇÃO DE GENOMAS ROMPENDO FRONTEIRAS
DOI:
https://doi.org/10.18554/acbiobras.v2i2.8674Palavras-chave:
doenças crônicas, edição gênica, biologia molecular, medicina genômicaResumo
As Doenças Cardiovasculares (DCVs) representam um conjunto de patologias que acometem o coração e os vasos sanguíneos, estas são consideradas como uma das
principais causas de mortalidade e morbidade em todo o mundo, contribuindo para
o aumento significativo de gastos dos sistemas de saúde. As DCVs são definidas como a incapacidade do coração em bombear sangue, oxigênio e nutrientes para os órgãos e tecidos. São patologias de etiologia multifatorial e seu desenvolvimento é relacionado, principalmente, aos fatores genéticos. Atualmente, sabe-se que
determinadas variações gênicas podem implicar na susceptibilidade e progressão da doença. Toda via, ainda não existem métodos de prevenção e diminuição do ritmo de progressão das DCVs com base nos fatores genéticos. Assim, este estudo visa correlacionar a técnica CRISPR/Cas9 às DCVs. O CRISPR/Cas9 é um sistema
que se mostra útil na modulação do genoma e edição dos fatores genéticos, este pode ser aplicado na correção das variantes genéticas predizentes à doença, através da inserção ou deleção de bases nitrogenadas do genoma, bem como ser utilizado
na diferenciação de células-tronco em cardiomiócitos para a correção de DCVs. O
CRISPR/Cas9 é a mais recente e notável ferramenta capaz de editar o DNA, possibilitando a terapia gênica para o controle de inúmeras patologias, incluindo as
cardiovasculares.
Referências
(1) Pirani N, Khiavi F. 2017. Population Attributable Fraction for Cardiovascular
Diseases Risk Factors in Selected Countries: A comparative study. Mater Socio
Medica. 29 (1): 35.
(2) Rocha RM, Martins W de A. 2017. Manual de prevenção cardiovascular. 1 ed.
Ricardo Mourilhe Rocha W de AM, editor. Rio de Janeiro: SOCERJ - Sociedade
de Cardiologia do Estado do Rio de Janeiro; 5 – 93 p.
(3) Arend MC, Pereira JO, Markoski MM. 2016. The CRISPR/Cas9 System and
the Possibility of Genomic Edition for Cardiology. Arq Bras Cardiol. 108 (1): 81–
3.
(4) Organization WH. Global Atlas on cardiovascular disease prevention and
control. Shanthi Mendis PP and BN. 2011. editor. Vol. 1, World Health Organization. Geneva. 3–155 p.
(5) Nordestgaard BG. 2016. Triglyceride-Rich Lipoproteins and Atherosclerotic
Cardiovascular Disease. Circ Res. 118 (4): 547–63.
(6) Huang L, Hua Z, Xiao H, Cheng Y, Xu K, Gao Q, et al. 2017. CRISPR/Cas9-
mediated ApoE-/-and LDLR-/-double gene knockout in pigs elevates serum LDL-C and TC levels. Oncotarget. 8 (23): 37751–60.
(7) Kathiresan S, Srivastava D. 2012. Genetics of Human Cardiovascular Disease.
Cell. 148 (6): 1242–57.
(8) Manson JE, Bassuk SS. 2015. Biomarkers of cardiovascular disease risk in
women. Metabolism. 64 (3): S33–9.
(9) Dittrich J, Beutner F, Teren A, Thiery J, Burkhardt R, Scholz M, et al. 2019.
Plasma levels of apolipoproteins C-III, A-IV, and E are independently associated
with stable atherosclerotic cardiovascular disease. Atherosclerosis. 281: 17–24.
(10) Schumacher T, Benndorf RA. 2017. ABC Transport Proteins in Cardiovascular Disease—A Brief Summary. Molecules. 22 (4): 589.
(11) Yu X, Qian K, Jiang N, Zheng X, Cayabyab FS, Tang C. 2014. ABCG5/ABCG8 in cholesterol excretion and atherosclerosis. Clin Chim Acta. 428:82–8.
(12) Iacocca MA, Wang J, Sarkar S, Dron JS, Lagace T, McIntyre AD, et al. 2018.
Whole-Gene Duplication of PCSK9 as a Novel Genetic Mechanism for Severe
Familial Hypercholesterolemia. Can J Cardiol. 34 (10): 1316–24.
(13) Marian AJ, Braunwald E. 2017. Hypertrophic Cardiomyopathy. Circ Res. 121
(7): 749–70.
(14) Sabater-Molina M, Pérez-Sánchez I, Hernández del Rincón JP, Gimeno JR.
2018. Genetics of hypertrophic cardiomyopathy: A review of current state. Clin
Gene. 93 (1): 3–14.
(15) Marsiglia JDC, Credidio FL, de Oliveira TGM, Reis RF, Antunes M de O, de
Araujo AQ, et al. 2013. Screening of MYH7, MYBPC3, and TNNT2 genes in
Brazilian patients with hypertrophic cardiomyopathy. Am Heart J. 166 (4): 775–82.
(16) Sedaghat-Hamedani F, Kayvanpour E, Tugrul OF, Lai A, Amr A, Haas J, et
al. 2018. Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals. Clin Res Cardiol. 107 (1):
30–41.
(17) Wang Y, Du X, Zhou Z, Jiang J, Zhang Z, Ye L, et al. 2016. A gain-of-function
ACTC1 3′UTR mutation that introduces a miR-139-5p target site may be associated with a dominant familial atrial septal defect. Sci Rep. 6 (1): 25404.
(18) Despond EA, Dawson JF. 2018. Classifying Cardiac Actin Mutations
Associated With Hypertrophic Cardiomyopathy. Front Physiol. 9 (April): 1–6.
(19) Nijak A, Alaerts M, Kuiperi C, Corveleyn A, Suys B, Paelinck B, et al. 2018.
Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1
mutation. Eur J Med Genet. 61 (1): 8–10.
(20) Lu X-L, Yao X-L, Yan C-Y, Wan Q-L, Li Y-M. 2016. Functional role of NKX2-5 and Smad6 expression in developing rheumatic heart disease. Eur Rev Med Pharmacol Sci. 20 (4): 715–20.
(21) Van Berlo JH, Aronow BJ, Molkentin JD. 2013. Parsing the Roles of the
Transcription Factors GATA-4 and GATA-6 in the Adult Cardiac Hypertrophic
Response. Sadayappan S, editor. PLoS One. 8 (12): e84591.
(22) Dixit R, Narasimhan C, Balekundri VI, Agrawal D, Kumar A, Mohapatra B.
2018. Functionally significant, novel GATA4 variants are frequently associated
with Tetralogy of Fallot. Hum Mutat. 39 (12): 1957–72.
(23) Steimle JD, Moskowitz IP. 2017. TBX5. In: Current Topics in Developmental
Biology. p. 195–221.
(24) Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. 2007.
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women:
2007 Update. Circulation. 115 (11): 1481–501.
(25) Organização Mundial de Saúde. OPAS/OMS Brasil - Doenças cardiovasculares. [cited 2018 May 22]. Available from: https://www.paho.org/bra/index.php?option=com_content&view=article&id=5253:doencas-cardiovasculares&Itemid=839
(26) Brant LCC, Nascimento BR, Passos VMA, Duncan BB, Bensenõr IJM, Malta
DC, et al. 2017. Variações e diferenciais da mortalidade por doença cardiovascular no Brasil e em seus estados, em 1990 e 2015: estimativas do Estudo Carga Global de Doença. Rev Bras Epidemiol. 20 (suppl 1): 116–28.
(27) Sander JD, Joung JK. 2014. CRISPR-Cas systems for editing, regulating and
targeting genomes. Nat Biotechnol. 32 (4): 347–55.
(28) Doudna JA, Charpentier E. 2014. The new frontier of genome engineering with CRISPR-Cas9. Science (80- ). 346 (6213): 1258096–1258096.
(29) Salsman J, Dellaire G. 2017. Precision genome editing in the CRISPR era.
Biochem Cell Biol. 95 (2): 187–201.
(30) García-Tuñón I, Hernández-Sánchez M, Ordoñez JL, Alonso-Pérez V, ÁlamoQuijada M, Benito R, et al. 2017. The CRISPR/Cas9 system efficiently reverts the tumorigenic ability of BCR/ABL in vitro and in a xenograft model of chronic myeloid leukemia. Oncotarget. 8 (16): 26027–40.
(31) Kang H, Minder P, Park MA, Mesquitta W-T, Torbett BE, Slukvin II. 2015.
CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides
Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus. Mol Ther - Nucleic Acids. 4 (12): e268.
(32) Yin Z, Cai M, Weng X, Liu Z, Zhang G. 2019. Porcine insulin receptor substrate 2 : molecular cloning , tissues distribution , and functions in hepatocyte and aortic endothelial cells. Pol J Vet Sci. 22 (3): 589–98.
(33) Chung JY, Ain QU, Song Y, Yong S-B, Kim Y-H. 2019. Targeted delivery of
CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance. Genome Res. 29 (9): 1442–52.
(34) Nguyen AH, Marsh P, Schmiess-heine L, Burke PJ, Lee A, Lee J. 2019. Cardiac tissue engineering : state-of-the-art methods and outlook 0: 57.
(35) Martinez-Lage M, Torres-Ruiz R, Rodriguez-Perales S. 2017. CRISPR/Cas9
Technology: Applications and Human Disease Modeling. In: Progress in Molecular
Biology and Translational Science. p. 23–48.
(36) Pan L, Sheng M, Huang Z, Zhu Z, Xu C, Teng L, et al. 2017. Zinc-finger
protein 418 overexpression protects against cardiac hypertrophy and fibrosis. Bader
M, editor. PLoS One. 12 (10): e0186635.
(37) Li Y, Yang D, Bai Y, Mo X, Huang W, Yuan W, et al. 2008. ZNF418, a novel
human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway.
Mol Cell Biochem. 310 (1–2): 141–51.
(38) Marczenke M, Piccini I, Mengarelli I, Fell J, Röpke A, Seebohm G, et al. 2017.
Cardiac subtype-specific modeling of Kv1.5 ion channel deficiency using human
pluripotent stem cells. Front Physiol. 8 (Jul): 1–11.
(39) Dehghani-Samani A, Madreseh-Ghahfarokhi S, Dehghani-Samani. 2019. A.
Mutations of voltage-gated ionic channels and risk of severe cardiac arrhythmias.
Acta Cardiol Sin. 35 (2): 99–110.
(40) Wang P, Liu Z, Zhang X, Li J, Sun L, Ju Z, et al. 2018. CRISPR/Cas9-mediated
gene knockout reveals a guardian role of NF-κB/RelA in maintaining the
homeostasis of human vascular cells. Protein Cell. 9 (11): 945–65.
(41) Karlgren M, Simoff I, Keiser M, Oswald S, Artursson P. 2018. CRISPR-Cas9:
A New Addition to the Drug Metabolism and Disposition Tool Box. Drug Metab
Dispos. 46 (11): 1776–86.
(42) Gonçalves GAR, Paiva R de MA. 2017. Gene therapy: advances, challenges
and perspectives. Einstein (São Paulo). 15 (3): 369–75.
(43) Mojica FJM, Díez-Villaseñor C, García-Martínez J, Soria E. 2005. Intervening
sequences of regularly spaced prokaryotic repeats derive from foreign genetic
elements. J Mol Evol. 60 (2): 174–82.
(44) Marraffini LA, Sontheimer EJ. 2010. CRISPR interference: RNA-directed
adaptive immunity in bacteria and archaea. Nat Rev Genet. 11 (3): 181–90.
(45) Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012.
A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial
Immunity. Science. 337 (6096): 816–21.
(46) Lino CA, Harper JC, Carney JP, Timlin JA. 2018. Delivering CRISPR: a
review of the challenges and approaches. Drug Deliv. 25 (1): 1234–57.
(47) Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, et al. 2008. Small CRISPR RNAs Guide Antiviral Defense in Prokaryotes. Science. 321 (5891): 960–4.
(48) Wright A V., Nuñez JK, Doudna JA. 2016. Biology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering. Cell. 164 (1–2): 29–44.
(49) Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA, Saunders SJ, et al. 2015. An updated evolutionary classification of CRISPR–Cas systems. Nat Rev Microbiol. 13 (11): 722–36.
(50) Makarova KS, Haft DH, Barrangou R, Brouns SJJ, Charpentier E, Horvath P, et al. 2011. Evolution and classification of the CRISPR–Cas systems. Nat Rev Microbiol. 9 (6): 467–77.
(51) Cribbs AP, Perera SMW. 2017. Science and bioethics of CRISPR-CAS9 gene editing: An analysis towards separating facts and fiction. Yale J Biol Med. 90 (4): 625–34.
(52) Motta BM, Pramstaller PP, Hicks AA, Rossini A. 2017. The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches. Stem Cells Int. 2017: 1–13.
(53) Musunuru K. 2017. Genome Editing. J Am Coll Cardiol. 70 (22): 2808–21.
(54) Carlos G, Caetano G, Matos HDEOS, Simão CR, Duarte RV, Barreto SA, et al. 2019. Técnica crispr-cas9 e sua utilização na área laboratorial. Brazilian J Surg Clin Res. 25 (1): 96–9.
(55) Yoshimi K, Kunihiro Y, Kaneko T, Nagahora H, Voigt B, Mashimo T. 2016. ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes. Nat Commun. 7 (1): 10431.
(56) Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, et al. 2008. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zincfinger nucleases. Nat Biotechnol. 26 (7): 808–16.
(57) Hsu PD, Lander ES, Zhang F. 2014. Development and Applications of CRISPR-Cas9 for Genome Engineering. Cell. 157 (6): 1262–78.
(58) Ma H, Marti-Gutierrez N, Park S-W, Wu J, Lee Y, Suzuki K, et al. 2017. Correction of a pathogenic gene mutation in human embryos. Nature. 548 (7668): 413–9.
(59) Birling M-C, Herault Y, Pavlovic G. 2017. Modeling human disease in rodents by CRISPR/Cas9 genome editing. Mamm Genome. 28 (7–8): 291–301.
(60) Boel A, De Saffel H, Steyaert W, Callewaert B, De Paepe A, Coucke PJ, et al. 2018. CRISPR/Cas9-mediated homology-directed repair by ssODNs in zebrafish induces complex mutational patterns resulting from genomic integration of repairtemplate fragments. Dis Model Mech. 11 (10): dmm035352.
(61) Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 8 (11): 2281–308.
(62) Finer M, Glorioso J. 2017. A brief account of viral vectors and their promise for gene therapy. Gene Ther. 24 (1): 1–2.
(63) Cho SW, Kim S, Kim Y, Kweon J, Kim HS, Bae S, et al. 2014. Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res. 24 (1): 132–41.
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