CRISPR-Cas9: el debate bioético más allá de la línea germinal
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https://doi.org/10.5294/pebi.2021.25.2.9Palabras clave:
Discusiones bioéticas, edición génica, efectividad, Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas, riesgos y beneficios, medición de riesgo, seguridadResumen
El sistema CRISPR-Cas9 es una tecnología de edición genética que, además de ampliar las posibilidades en investigación científica, despierta reflexiones asociadas a la dignidad humana, el control biológico, la terapia y la mejora genética. Se revisaron las discusiones bioéticas asociadas a los desafíos y las repercusiones que suscita su aplicación. Como resultado, los cuestionamientos bioéticos tienden a problematizar la aplicación en organismos no humanos, en la investigación básica y en la línea somática y germinal humana. Para concluir, falta incrementar los niveles de seguridad y efectividad para que los beneficios superen los riesgos y, de esta forma, sea posible disminuir las preocupaciones bioéticas y aumentar la credibilidad en el uso de la técnica.
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Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21. DOI: https://doi.org/10.1126/science.1225829
Leonova EI, Gainetdinov RR. CRISPR/Cas9 technology in translational biomedicine. Cell Physiol Biochem. 2020;54(3):354-70. DOI: https://doi.org/10.33594/000000224
Jefferson OA, Lang S, Williams K, Koellhofer D, Ballagh A, Warren B, et al. Mapping CRISPR-Cas9 public and commercial innovation using The Lens institutional toolkit. Transgenic Res. 2021;30(4):585-99. DOI: https://doi.org/10.1007/s11248-021-00237-y
Thaldar D, Botes M, Shozi B, Townsend B, Kinderlerer J. Human germline editing: Legal-ethical guidelines for South Africa. S Afr J Sci. 2020;116(9/10). DOI: https://doi.org/10.17159/sajs.2020/6760
Meshalkina DA, Glushchenko AS, Kysil EV, Mizgirev IV, Frolov A. SPCAS9-and LBCAS12A-mediated DNA editing produce different gene knockout outcomes in zebrafish embryos. Genes (Basel). 2020;11(7):740. DOI: https://doi.org/10.3390/genes11070740
Eissenberg JC. In our image: The ethics of CRISPR genome editing. Biomol Concepts. 2021;12(1):1-7. DOI: https://doi.org/10.1515/bmc-2021-0001
Greely HT. CRISPR’d babies: Human germline genome editing in the “He Jiankui affair”. J Law Biosci. 2019;6(1):111-83. DOI: https://doi.org/10.1093/jlb/lsz010
Escobar Triana JA, Aristizábal Tobler C. Los principios en la bioética: fuentes, propuestas y prácticas múltiples. Rev Colomb Bioética. 2015;6(3):76. DOI: https://doi.org/10.18270/rcb.v6i3.1057
Gamboa-Bernal GA. El ser humano y su dimensión bioética. Vol. 2. Chía (Cundinamarca): Universidad de la Sabana; 2014. DOI: https://doi.org/10.2307/j.ctvn1tc6x
Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213). DOI: https://doi.org/10.1126/science.1258096
Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169(12):5429-33. DOI: https://doi.org/10.1128/jb.169.12.5429-5433.1987
Mojica FJM, Díez-Villaseñor C, Soria E, Juez G. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol Microbiol. 2000;36(1):244-6. DOI: https://doi.org/10.1046/j.1365-2958.2000.01838.x
Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709-12. DOI: https://doi.org/10.1126/science.1138140
Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science. 2008;321(5891):960-4. DOI: https://doi.org/10.1126/science.1159689
Mojica FJM, Montoliu L. On the Origin of CRISPR-Cas Technology: From Prokaryotes to Mammals. Trends Microbiol. 2016;24(10):811-20. DOI: https://doi.org/10.1016/j.tim.2016.06.005
Hynes AP, Villion M, Moineau S. Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages. Nat Commun. 2014;5(1):4399. DOI: https://doi.org/10.1038/ncomms5399
Amitai G, Sorek R. CRISPR-Cas adaptation: Insights into the mechanism of action. Nat Rev Microbiol. 2016;14(2):67-76. DOI: https://doi.org/10.1038/nrmicro.2015.14
Lino CA, Harper JC, Carney JP, Timlin JA. Delivering crispr: A review of the challenges and approaches. Drug Deliv. 2018;25(1):1234-57.DOI: https://doi.org/10.1080/10717544.2018.1474964
Makarova KS, Wolf YI, Iranzo J, Shmakov SA, Alkhnbashi OS, Brouns SJJ, et al. Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol. 2020;18(2):67-83. DOI: https://doi.org/10.1038/s41579-019-0299-x
Song G, Jia M, Chen K, Kong X, Khattak B, Xie C, et al. CRISPR/Cas9: A powerful tool for crop genome editing. Crop J. 2016;4(2):75-82. DOI: https://doi.org/10.1016/j.cj.2015.12.002
Salsman J, Dellaire G. Precision genome editing in the CRISPR era. Biochem Cell Biol. 2017;95(2):187-201. DOI: https://doi.org/10.1139/bcb-2016-0137
Piergentili R, Del Rio A, Signore F, Umani Ronchi F, Marinelli E, Zaami S. CRISPR-Cas and its wide-ranging applications: From human genome editing to environmental implications, technical limitations, hazards and bioethical issues. Cells. 2021;10(5):969. DOI: https://doi.org/10.3390/cells10050969
Roh DS, Li EBH, Liao EC. CRISPR craft: DNA editing the reconstructive ladder. Plast Reconstr Surg. 2018;142(5):1355-64. DOI: https://doi.org/10.1097/PRS.0000000000004863
Cebrailoglu N, Yildiz AB, Akkaya O, Ozden Ciftci Y. CRISPR-Cas: Removing Boundaries of the Nature. Eur J Biol. 2019;78(2):75-81. DOI: https://doi.org/10.26650/EurJBiol.2019.0009
Liao HK, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, et al. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells. Nat Commun. 2015;6(1):6413. DOI: https://doi.org/10.1038/ncomms7413
Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science. 2017;357(6357):1303-7. DOI: https://doi.org/10.1126/science.aan4187
Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2016;34(1):78-83. DOI: https://doi.org/10.1038/nbt.3439
Wu Y, Liang D, Wang Y, Bai M, Tang W, Bao S, et al. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell. 2013;13(6):659-62. DOI: https://doi.org/10.1016/j.stem.2013.10.016
Schwank G, Koo BK, Sasselli V, Dekkers JF, Heo I, Demircan T, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013;13(6):653-8. DOI: https://doi.org/10.1016/j.stem.2013.11.002
Kennedy EM, Bassit LC, Mueller H, Kornepati AVR, Bogerd HP, Nie T, et al. Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. Virology. 2015;476:196-205. DOI: https://doi.org/10.1016/j.virol.2014.12.001
Tabebordbar M, Zhu K, Cheng JKW, Chew WL, Widrick JJ, Yan WX, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 2016;351(6271):407-11. DOI: https://doi.org/10.1126/science.aad5177
Palit SAL, van Dorp J, Vis D, Lieftink C, Linder S, Beijersbergen R, et al. A kinome-centered CRISPR-Cas9 screen identifies activated BRAF to modulate enzalutamide resistance with potential therapeutic implications in BRAF-mutated prostate cancer. Sci Rep. 2021;11(1). DOI: https://doi.org/10.1038/s41598-021-93107-w
Chan K, Tong AHY, Brown KR, Mero P, Moffat J. Pooled CRISPR-based genetic screens in Mammalian cells. J Vis Exp. 2019;2019(151). DOI: https://doi.org/10.3791/59780
Laboratory H. About Lulu and Nana: Twin Girls Born Healthy After Gene Surgery As Single-Cell Embryos - YouTube; 2019. Disponible en: https://www.youtube.com/watch?v=th0vnOmFltc
Reem NT, Van Eck J. Application of CRISPR/Cas9-mediated gene editing in tomato. Methods Mol Biol. 2019;1917:171-82. DOI: https://doi.org/10.1007/978-1-4939-8991-1_13
Andersson M, Turesson H, Olsson N, Fält AS, Ohlsson P, Gonzalez MN, et al. Genome editing in potato via CRISPR-Cas9 ribonucleoprotein delivery. Physiol Plant. 2018;164(4):378-84. DOI: https://doi.org/10.1111/ppl.12731
Chandrasekaran J, Brumin M, Wolf D, Leibman D, Klap C, Pearlsman M, et al. Development of broad virus resistance in non-transgenic cucumber using CRISPR/Cas9 technology. Mol Plant Pathol. 2016;17(7):1140-53. DOI: https://doi.org/10.1111/mpp.12375
Arazoe T, Miyoshi K, Yamato T, Ogawa T, Ohsato S, Arie T, et al. Tailor-made CRISPR/Cas system for highly efficient targeted gene replacement in the rice blast fungus. Biotechnol Bioeng. 2015;112(12):2543-9. DOI: https://doi.org/10.1002/bit.25662
Svitashev S, Young JK, Schwartz C, Gao H, Falco SC, Cigan AM. Targeted mutagenesis, precise gene editing, and site-specific gene insertion in maize using Cas9 and guide RNA. Plant Physiol. 2015;169(2):931-45. DOI: https://doi.org/10.1104/pp.15.00793
Eş I, Gavahian M, Marti-Quijal FJ, Lorenzo JM, Mousavi Khaneghah A, Tsatsanis C, et al. The application of the CRISPR-Cas9 genome editing machinery in food and agricultural science: Current status, future perspectives, and associated challenges. Biotechnol Adv. 2019;37(3):410-21. DOI: https://doi.org/10.1016/j.biotechadv.2019.02.006
Ouyang B, Gu X, Holford P. Plant genetic engineering and biotechnology: a sustainable solution for future food security and industry. Plant Growth Regul. 2017;83(2):171-3. DOI: https://doi.org/10.1007/s10725-017-0300-5
Ma X, Zhu Q, Chen Y, Liu YG. CRISPR/Cas9 platforms for genome editing in plants: Developments and applications. Mol Plant. 2016;9(7):961-74. DOI: https://doi.org/10.1016/j.molp.2016.04.009
Li Y, Li W, Li J. The CRISPR/Cas9 revolution continues: From base editing to prime editing in plant science. J Genet Genomics. 2021;5(1):1673-8527 DOI: https://doi.org/10.1016/j.jgg.2021.05.001
Santaló J, Casado M. Document sobre bioètica i edició genòmica en humans. 2016. Diponible en: http://hdl.handle.net/2445/105022
Brokowski C, Adli M. CRISPR Ethics: Moral considerations for applications of a powerful tool. JMB. 2019;431(1):88-101. DOI: https://doi.org/10.1016/j.jmb.2018.05.044
The Royal Society, National Academy of Sciences, National Academy of Medicine, International Commission on the Clinical Use of Human Germline Genome Editing. Heritable Human Genome Editing. Washington, D.C., DC: National Academies Press; 2021. Disponible en: https://www.nap.edu/catalog/25665/heritable-human-genome-editing
Ayanoğlu FB, Elçİn AE, Elçİn YM. Bioethical issues in genome editing by CRISPR-Cas9 technology. Turkish J Biol. 2020;44(2):110-20. DOI: https://doi.org/10.3906/biy-1912-52
Shinwari ZK, Tanveer F, Khalil AT. Ethical issues regarding CRISPR-mediated genome editing. Curr Issues Mol Biol. 2018;26:103-10. DOI: https://doi.org/10.21775/cimb.026.103
Zhang J, Khazalwa EM, Abkallo HM, Zhou Y, Nie X, Ruan J, et al. The advancements, challenges, and future implications of the CRISPR/Cas9 system in swine research. J Genet Genomics. 2021;48(5):347-60. DOI: https://doi.org/10.1016/j.jgg.2021.03.015
El-Mounadi K, Morales-Floriano ML, Garcia-Ruiz H. Principles, applications, and biosafety of plant genome editing using CRISPR-Cas9. Front Plant Sci. 2020;11:56. DOI: https://doi.org/10.3389/fpls.2020.00056
Lima NS. CRISPR/Cas9: Reflexiones bioéticas sobre las modificaciones genómicas. J Basic Appl Gen. 2018;29(1):25-7. Disponible en: https://sag.org.ar/jbag/wp-content/uploads/2019/09/BAG_VXXIX_1_2018_ART1_WEB.pdf
Cathomen T, Schüle S, Schüßler-Lenz M, Abou-El-Enein M. The human genome editing race: Loosening regulatory standards for commercial advantage? Trends Biotechnol. 2019;37(2):120-3. DOI: https://doi.org/10.1016/j.tibtech.2018.06.005
Alonso M, Anomaly J, Savulescu J. Gene editing: Medicine or enhancement. Ramon Llull J Appl Ethics. 2020;(11):259-76. Disponible en: https://raco.cat/index.php/rljae/article/view/368740
Cribbs AP, Perera SMW. Science and bioethics of CRISPR-Cas9 gene editing: An analysis towards separating facts and fiction. Yale J Biol Med. 2017;90(4):625-34. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29259526/
Zeps N, Lysaght T, Chadwick R, Erler A, Foo R, Giordano S, et al. Ethics and regulatory considerations for the clinical translation of somatic cell human epigenetic editing. Stem Cell Reports. 2021;16(7):1652-5. DOI: https://doi.org/10.1016/j.stemcr.2021.06.004
Peters T. Flashing the yellow traffic light: Choices forced upon us by gene editing technologies. Theol Sci. 2019;17(1):79-89. DOI: https://doi.org/10.1080/14746700.2019.1557807
Savulescu J, Pugh J, Douglas T, Gyngell C. The moral imperative to continue gene editing research on human embryos. Protein Cell. 2015;6(7):476-9. https://doi.org/10.1007/s13238-015-0184-y
Santillán-Doherty P, Grether-González P, Medina-Arellano M de J, Chan S, Tapia-Ibargüengoitia R, Brena-Sesma I, et al. Reflexiones sobre la ingeniería genética: a propósito del nacimiento de gemelas sometidas a edición génica. Gac Med Mex. 2020;156(1):53-9. DOI: https://doi.org/10.24875/GMM.19005182
Gumer JM. The wisdom of germline editing: An ethical analysis of the use of CRISPR-Cas9 to edit human embryos. New Bioeth. 2019;25(2):137-52. DOI: https://doi.org/10.1080/20502877.2019.1606151
De Lecuona I, Casado M, Marfany G, Lopez Baroni M, Escarrabill M. Gene editing in humans: Towards a global and inclusive debate for responsible research. Yale J Biol Med. 2017;90(4):673-681. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29259532/
Greenfield A. Making sense of heritable human genome editing: Scientific and ethical considerations. Prog Mol Biol Transl Sci. 2021;182:1-28. DOI: https://doi.org/10.1016/bs.pmbts.2020.12.008
Eckerstorfer MF, Dolezel M, Heissenberger A, Miklau M, Reichenbecher W, Steinbrecher RA, Waßmann F. An EU perspective on biosafety considerations for plants developed by genome editing and other new genetic modification techniques (nGMs). Front Bioeng Biotechnol. 2019;7:31. DOI: https://doi.org/10.3389/fbioe.2019.00031
Ledford H. CRISPR, the disruptor. Nature. 2015;522(7554):20-4. DOI: https://doi.org/10.1038/522020a
Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, et al. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat Biotechnol. 2018;36(11):1062-6. DOI: https://doi.org/10.1038/nbt.4245
Dolgin Elie. Finding the CRISPR off-switch. Nature; 2020. Disponible en: https://media.nature.com/original/magazine-assets/d41586-020-00053-0/d41586-020-00053-0.pdf
Tanihara F, Hirata M, Thi Nguyen N, Anh Le Q, Hirano T, Otoi T. Generation of viable PDX1 gene-edited founder pigs as providers of nonmosaics. Mol Reprod Dev. 2020;87(4):471-81. DOI: https://doi.org/10.1002/mrd.23335
Wang K, Tang X, Xie Z, Zou X, Li M, Yuan H, et al. CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs. Transgenic Res. 2017;26(6):799-805. DOI: https://doi.org/10.1007/s11248-017-0044-z
Juth N Germline genetic modification, CRSIPR, and human identity: Can genetics turn you into someone else? Ethics, Med Public Health. 2016;2(3):416-25. DOI: https://doi.org/10.1016/j.jemep.2016.05.003
Schaefer KA, Wu W-H, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Unexpected mutations after CRISPR-Cas9 editing in vivo. Nat Methods. 2017;14(6):547-548. DOI: https://doi.org/10.1038/nmeth.4293
Polcz S, Lewis A. CRISPR-Cas9 and the non-germline non-controversy. J Law Biosci. 2016;3(2):413-25. DOI: https://doi.org/10.1093/jlb/lsw016
Cyranoski D, Ledford H. Genome-edited baby claim provokes international outcry. Nature. 2018;563(7733):607-8. DOI: https://doi.org/10.1038/d41586-018-07545-0
Wright AV, Nuñez JK, Doudna JA. Biology and applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering. Cell. 2016;164(1-2):29-44. DOI: https://doi.org/10.1016/j.cell.2015.12.035
Krimsky S. Breaking the germline barrier in a moral vacuum. Account Res. 2019;26(6):351-68. DOI: https://doi.org/10.1080/08989621.2019.1644171
Schaefer G. Rogue science strikes again: The case of the first gene-edited babies; 2018. Disponible en: https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684
Resnik DB. Bioethical issues in providing financial incentives to research participants. Medicoleg Bioeth. 2015;5:35-41. DOI: https://doi.org/10.2147/MB.S70416
ACNUDH - Asamblea General. Declaración Universal sobre el genoma humano y los derechos humanos; 1997. Disponible en: https://www.ohchr.org/SP/ProfessionalInterest/Pages/HumanGenomeAndHumanRights.aspx
Dantas CHF, Ferraz CV, Falcão JR de M. La protección de la diversidad en el patrimonio genético: implicaciones bioéticas y jurídicas en el uso de CRISPR-Cas9 como herramienta de edición genómica en humanos. Rev Bioet Derecho. 2020;1(49):77-91. DOI: https://doi.org/10.1344/rbd2020.49.29384
Xu M. CCR5-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool. Cell Biosci. 2020;10:48. DOI: https://doi.org/10.1186/s13578-020-00410-6
Johnston J. Shaping the CRISPR gene-editing debate: Questions about enhancement and germline modification. Perspect Biol Med. 2020;63(1):141-54. DOI: https://doi.org/10.1353/pbm.2020.0011
Gamboa-Bernal GA. La edición de genes a estudio: los problemas bioéticos que puede tener esta nueva tecnología. Pers Bioet. 2016;20(2):12-13. DOI: https://doi.org/10.5294/pebi.2016.20.2.1
Martínez, Ma. de la Luz Casas, Virginia Aspe Armella, Stéphanie Derive, M. Lourdes González-del-Rincón, Hugo S. Ramírez García, Alberto Ross, et al. Reflexión bioética interdisciplinaria en torno a la edición genética con CRISPR-Cas en línea germinal en el contexto del transhumanismo. Revista de Filosofía Open Insight. 2019;10(18):185-213. Disponible en: https://www.redalyc.org/journal/4216/421660973007/html/
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