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Vol. 9 Núm. 1 (2024)
Volumen Especial Investigación en CANCER GASTRICO retos y resultados

Artículos de Revisión

Nuevos Enfoques en la Cura del VIH-1: Técnicas de Edición Genética y Represión Génica. Revisión de Tema

https://doi.org/10.19053/uptc.2744953X.17659

Publicado 05-06-2024

Nicolas Alejandro Castilla Salcedo
Universidad Industrial de Santander image/svg+xml

Resumen

Introducción: El reto global del virus de la inmunodeficiencia humana tipo 1, afectando a 39 millones de personas, persiste pese al éxito de la terapia antirretroviral de gran actividad . La resistencia viral, toxicidad a largo plazo y cargas económicas han impulsado la exploración de técnicas de edición genética y represión de expresión génica como soluciones potenciales. Objetivo: Realizar un análisis exhaustivo de investigaciones recientes siguiendo las pautas de Elementos de Informes Preferidos para Revisiones Sistemáticas y Metaanálisis, centrándose en la modificación genética y la represión genética en muestras infectadas por VIH-1. Métodos: Se identificaron 413 artículos, de los cuales 76 cumplían criterios. Los criterios de inclusión incluyeron estudios sobre edición de genes relacionados con expresión del VIH-1 (2019-2023), enfatizando la represión de CCR5/CXCR4. Las exclusiones se aplicaron en pruebas débiles, sin eficacia práctica y sin relevancia al VIH-1 o las herramientas genéticas, así como los duplicados y los artículos que no eran de acceso libre. Resultados: Hay estrategias que muestran promisorias capacidades para reducir la cronicidad de la infección, pero se enfrentan a desafíos notables como los efectos fuera del objetivo, dilemas éticos en la edición in vivo, ex vivo y de la línea germinal, y variabilidad en la eficacia entre estudios. Remarca la necesidad de evaluación, mejorar técnicas y desarrollar métodos de administración más eficaces. Conclusiones: Esta revisión de tema destaca avances recientes en edición genética para VIH-1. Aunque prometedores, los desafíos demandan investigación continua para aprovechar plenamente estas estrategias en la búsqueda de una cura eficaz.

Palabras clave

VIH-1, Interferencia de ARN, miARN, siARN, Silenciador del Gen, Receptor CCR5, Sistemas CRISPR-Cas

PDF (English)

Biografía del autor/a

Nicolas Alejandro Castilla Salcedo

Estudiante de Medicina. Universidad Industrial de Santander

Citas

  1. Joint United Nations Programme on HIV/AIDS (UNAIDS). Latest statistics on the state of the HIV/AIDS epidemic. Global HIV Statistics (Internet). 2022. Available from: https://www.unaids.org/en/resources/fact-sheet. Accessed: July 1, 2023.
  2. Abana CZY, Lamptey H, Bonney EY, Kyei GB. HIV cure strategies: which ones are appropriate for Africa? Cellular and Molecular Life Sciences. 2022;79(8).
  3. Sadowski I, Hashemi FB. Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs. Cellular and Molecular Life Sciences. 2019;76(18):3583-600.
  4. Jai J, Shirleen D, Hanbali C, Wijaya P, Anginan TB, Husada W, et al. Multiplexed shRNA-miRs as a candidate for anti HIV-1 therapy: strategies, challenges, and future potential. J Genet Eng Biotechnol. 28 de diciembre de 2022;20(1):172.
  5. Lee C. CRISPR/Cas9-Based Antiviral Strategy: Current Status and the Potential Challenge. Molecules. 5 de abril de 2019;24(7):1349.
  6. Nguyen H, Wilson H, Jayakumar S, Kulkarni V, Kulkarni S. Efficient Inhibition of HIV Using CRISPR/Cas13d Nuclease System. Viruses. 2021;13(9).
  7. Sonti S, Sharma AL, Tyagi M. HIV-1 persistence in the CNS: Mechanisms of latency, pathogenesis and an update on eradication strategies. Virus Research. 2021;303.
  8. Dash PK, Kaminski R, Bella R, Su H, Mathews S, Ahooyi TM, Chen C, Mancuso P, Sariyer R, Ferrante P, Donadoni M, Robinson JA, Sillman B, Lin Z, Hilaire JR, Banoub M, Elango M, Gautam N, Mosley RL, Poluektova LY, McMillan J, Bade AN, Gorantla S, Sariyer IK, Burdo TH, Young WB, Amini S, Gordon J, Jacobson JM, Edagwa B, Khalili K, Gendelman HE. Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nat Commun. 2019 Jul 2;10(1):2753. doi: 10.1038/s41467-019-10366-y. PMID: 31266936; PMCID: PMC6606613.
  9. Zhang J, Han J, Li H, Li Z, Zou P, Li J, et al. Lymphocyte Membrane- and 12p1-Dual-Functionalized Nanoparticles for Free HIV-1 Trapping and Precise siRNA Delivery into HIV-1-Infected Cells. Adv Sci (Weinh). abril de 2023;10(10):e2300282.
  10. Scopus - Document details - Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy | Signed in (Internet). (citado 25 de junio de 2023). Disponible en: https://www.scopus.com/record/display.uri?eid=2-s2.0-85124071557&origin=resultslist&sort=plf-f&src=s&sid=7d2b7131bc44f700be93875cc598ce15&sot=b&sdt=b&s=TITLE-ABS-KEY%28CCR5+AND+interference%29&sl=26&sessionSearchId=7d2b7131bc44f700be93875cc598ce15
  11. Olson A, Basukala B, Wong WW, Henderson AJ. Targeting HIV-1 proviral transcription. Current Opinion in Virology. 2019;38:89-96.
  12. Ndung'u T, McCune JM, Deeks SG. Why and where an HIV cure is needed and how it might be achieved. Nature. 2019 Dec;576(7787):397-405. doi: 10.1038/s41586-019-1841-8. Epub 2019 Dec 18. PMID: 31853080; PMCID: PMC8052635.
  13. Ahlenstiel CL, Symonds G, Kent SJ, Kelleher AD. Block and Lock HIV Cure Strategies to Control the Latent Reservoir. Front Cell Infect Microbiol. 14 de agosto de 2020;10:424.
  14. Killingsworth L, Spudich S. Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection. Semin Immunopathol. 1 de septiembre de 2022;44(5):709-24.
  15. Xiao Q, Guo D, Chen S. Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy. Front Cell Infect Microbiol. 22 de marzo de 2019;9:69.
  16. Xiao Q, Chen S, Wang Q, Liu Z, Liu S, Deng H, et al. CCR5 editing by Staphylococcus aureus Cas9 in human primary CD4+ T cells and hematopoietic stem/progenitor cells promotes HIV-1 resistance and CD4+ T cell enrichment in humanized mice. Retrovirology. 11 de junio de 2019;16(1):15.
  17. Darcis G, Binda CS, Klaver B, Herrera-Carrillo E, Berkhout B, Das AT. The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape. Viruses-Basel. 13 de marzo de 2019;11(3):255.
  18. Darcis G, Binda CS, Klaver B, Herrera-Carrillo E, Berkhout B, Das AT. The Impact of HIV-1 Genetic Diversity on CRISPR-Cas9 Antiviral Activity and Viral Escape. Viruses. 2019 Mar 13;11(3):255. doi: 10.3390/v11030255. PMID: 30871200; PMCID: PMC6466431.
  19. Müller TG, Zila V, Müller B, Kräusslich HG. Nuclear Capsid Uncoating and Reverse Transcription of HIV-1. Annual Review of Virology. 2022;9(1):261-84.
  20. 1. Zila V, Margiotta E, Turoňová B, Müller TG, Zimmerli CE, Mattei S, et al. Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell. 18 de febrero de 2021;184(4):1032-1046.e18.
  21. Sanches-da-Silva GDN, Sales Medeiros LF, Lima FM. The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy. Int J Genomics. 21 de agosto de 2019;2019:8458263.
  22. Sheykhhasan M, Foroutan A, Manoochehri H, Khoei SG, Poondla N, Saidijam M. Could gene therapy cure HIV? Life Sciences. 2021;277.
  23. Hashmat R, Yousaf MZ, Rahman Z, Anjum KM, Yaqub A, Imran M. CRISPR-CAS Replacing Antiviral Drugs against HIV: An Update. Crit Rev Eukaryot Gene Expr. 2020;30(1):77-83.
  24. Henderson LJ, Reoma LB, Kovacs JA, Nath A. Advances toward curing HIV-1 infection in tissue reservoirs. Journal of Virology. 2020;94(3).
  25. Vanhamel J, Bruggemans A, Debyser Z. Establishment of latent HIV-1 reservoirs: what do we really know? J Virus Erad. 5(1):3-9.
  26. Bhowmik R, Chaubey B. CRISPR/Cas9: a tool to eradicate HIV-1. Aids Res Ther. 1 de diciembre de 2022;19(1):58.
  27. Moranguinho I, Valente ST. Block-And-Lock: New Horizons for a Cure for HIV-1. Viruses-Basel. diciembre de 2020;12(12):1443.
  28. Pluta A, Jaworski JP, Cortés-Rubio CN. Balance between retroviral latency and transcription: Based on hiv model. Pathogens. 2021;10(1):1-26.
  29. Chinniah R, Adimulam T, Nandlal L, Arumugam T, Ramsuran V. The Effect of miRNA Gene Regulation on HIV Disease. Frontiers in Genetics. 2022;13.
  30. Bertrand L, Velichkovska M, Toborek M.. J Neuroimmune Pharmacol. 1 de marzo de 2021;16(1):74-89.
  31. Killingsworth L, Spudich S. Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection. Semin Immunopathol. 1 de septiembre de 2022;44(5):709-24.
  32. Wallet C, De Rovere M, Van Assche J, Daouad F, De Wit S, Gautier V, et al. Microglial Cells: The Main HIV-1 Reservoir in the Brain. Frontiers in Cellular and Infection Microbiology. 2019;9.
  33. Hussein M, Molina MA, Berkhout B, Herrera-Carrillo E. A CRISPR-Cas Cure for HIV/AIDS. Int J Mol Sci. enero de 2023;24(2):1563.
  34. Binda CS, Klaver B, Berkhout B, Das AT. CRISPR-Cas9 Dual-gRNA Attack Causes Mutation, Excision and Inversion of the HIV-1 Proviral DNA. Viruses-Basel. marzo de 2020;12(3):330.
  35. Colby DJ, Trautmann L, Pinyakorn S, et al. Time to Viral Rebound After Interruption of Modern Antiretroviral Therapies. J Infect Dis. 2022 Mar 3;225(5):748-758. doi: 10.1093/infdis/jiab008. PMID: 34609303.
  36. Verdikt R, Darcis G, Ait-Ammar A, Van Lint C. Applications of CRISPR/Cas9 tools in deciphering the mechanisms of HIV-1 persistence. Curr Opin Virol. octubre de 2019;38:63-9.
  37. Chen J, Zhou T, Zhang Y, Luo S, Chen H, Chen D, et al. The reservoir of latent HIV. Frontiers in Cellular and Infection Microbiology. 2022;12.
  38. Bandera A, Gori A, Clerici M, Sironi M. Phylogenies in ART: HIV reservoirs, HIV latency and drug resistance. Curr Opin Pharmacol. 2019 Oct;48:24-32. doi: 10.1016/j.coph.2019.03.003. Epub 2019 Apr 28. PMID: 31029861.
  39. Yoder KE. A CRISPR/Cas9 library to map the HIV-1 provirus genetic fitness. Acta Virol. 2019;63(2):129-38.
  40. Das AT, Binda CS, Berkhout B. Elimination of infectious HIV DNA by CRISPR-Cas9. Curr Opin Virol. octubre de 2019;38:81-8.
  41. Chung CH, Allen AG, Atkins AJ, Sullivan NT, Homan G, Costello R, et al. Safe CRISPR-Cas9 Inhibition of HIV-1 with High Specificity and Broad-Spectrum Activity by Targeting LTR NF-κB Binding Sites. Molecular Therapy - Nucleic Acids. 2020;21:965-82.
  42. Delannoy A, Poirier M, Bell B. Cat and mouse: HIV transcription in latency, immune evasion and cure/remission strategies. Viruses. 2019;11(3).
  43. Maina EK, Adan AA, Mureithi H, Muriuki J, Lwembe RM. A Review of Current Strategies Towards the Elimination of Latent HIV-1 and Subsequent HIV-1 Cure. Curr HIV Res. 2021;19(1):14-26.
  44. Atkins AJ, Allen AG, Dampier W, Haddad EK, Nonnemacher MR, Wigdahl B. HIV-1 cure strategies: why CRISPR? Expert Opin Biol Ther. junio de 2021;21(6):781-93.
  45. Li J. Advances toward a cure for HIV: getting beyond n=2. Top Antivir Med. 2020 Jan;27(4):91-95. PMID: 32224499; PMCID: PMC7162679.
  46. Leite TF, Delatorre E, Côrtes FH, Ferreira ACG, Cardoso SW, Grinsztejn B, et al. Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection. Frontiers in Microbiology [Internet]. 2019 [citado 24 de febrero de 2024];10. Disponible en: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00145
  47. Baddeley HJE, Isalan M. The Application of CRISPR/Cas Systems for Antiviral Therapy. Front Genome Edit. 13 de octubre de 2021;3:745559.
  48. Scheller SH, Rashad Y, Saleh FM, Willingham KA, Reilich A, Lin D, et al. Biallelic, Selectable, Knock-in Targeting of CCR5 via CRISPR-Cas9 Mediated Homology Directed Repair Inhibits HIV-1 Replication. Front Immunol. 2022;13:821190.
  49. Vergara-Mendoza M, Gomez-Quiroz LE, Miranda-Labra RU, Fuentes-Romero LL, Romero-Rodriguez DP, Gonzalez-Ruiz J, et al. Regulation of Cas9 by viral proteins Tat and Rev for HIV-1 inactivation. Antiviral Res. agosto de 2020;180:104856.
  50. Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther. 2020 Jan 3;5(1):1. doi: 10.1038/s41392-019-0089-y. PMID: 32296011; PMCID: PMC6946647.
  51. Herskovitz J, Hasan M, Patel M, Blomberg WR, Cohen JD, Machhi J, et al. CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination. EBioMedicine. noviembre de 2021;73:103678.
  52. Herrera-Carrillo E, Gao Z, Berkhout B. CRISPR therapy towards an HIV cure. Brief Funct Genomics. mayo de 2020;19(3):201-8.
  53. Lian X, Seiger KW, Parsons EM, Gao C, Sun W, Gladkov GT, et al. Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy. Cell Host and Microbe. 2023;31(1):83-96.e5.
  54. Watters KE, Kirkpatrick J, Palmer MJ, Koblentz GD. The CRISPR revolution and its potential impact on global health security. Pathogens and Global Health. 2021;115(2):80-92.
  55. Mohammadzadeh I, Qujeq D, Yousefi T, Ferns GA, Maniati M, Vaghari-Tabari M. CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity. IUBMB Life. agosto de 2020;72(8):1603-21.
  56. Escalona-Noguero C, Lopez-Valls M, Sot B. CRISPR/Cas technology as a promising weapon to combat viral infections. Bioessays. abril de 2021;43(4):e2000315.
  57. Zhang Z, Hou W, Chen S. Updates on CRISPR-based gene editing in HIV-1/AIDS therapy. Virol Sin. febrero de 2022;37(1):1-10.
  58. Najafi S, Tan SC, Aghamiri S, Raee P, Ebrahimi Z, Jahromi ZK, et al. Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections. Biomed Pharmacother. abril de 2022;148:112743.
  59. Maslennikova A, Mazurov D. Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection. Frontiers in Cellular and Infection Microbiology. 2022;12.
  60. Armstrong DA, Hudson TR, Hodge CA, Hampton TH, Howell AL, Hayden MS. PlmCas12e (CasX2) cleavage of CCR5: impact of guide RNA spacer length and PAM sequence on cleavage activity. RNA Biology. 31 de diciembre de 2023;20(1):296-305.
  61. Yin L, Zhao F, Sun H, Wang Z, Huang Y, Zhu W, et al. CRISPR-Cas13a Inhibits HIV-1 Infection. Mol Ther-Nucl Acids. 4 de septiembre de 2020;21:147-55.
  62. Xue Y, Chen Z, Zhang W, Zhang J. Engineering CRISPR/Cas13 System against RNA Viruses: From Diagnostics to Therapeutics. Bioengineering-Basel. julio de 2022;9(7):291.
  63. Ophinni Y, Miki S, Hayashi Y, Kameoka M. Multiplexed tat-Targeting CRISPR-Cas9 Protects T Cells from Acute HIV-1 Infection with Inhibition of Viral Escape. Viruses. 28 de octubre de 2020;12(11):1223.
  64. Mohamed H, Gurrola T, Berman R, Collins M, Sariyer IK, Nonnemacher MR, et al. Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy. Frontiers in Immunology. 2022;12.
  65. Fan M, Berkhout B, Herrera-Carrillo E. A combinatorial CRISPR-Cas12a attack on HIV DNA. MolTher-Methods Clin Dev. 9 de junio de 2022;25:43-51.
  66. Khanal S, Cao D, Zhang J, Zhang Y, Schank M, Dang X, et al. Synthetic gRNA/Cas9 Ribonucleoprotein Inhibits HIV Reactivation and Replication. Viruses. 28 de agosto de 2022;14(9):1902.
  67. Liu Y, Jeeninga RE, Klaver B, Berkhout B, Das AT. Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line. Viruses-Basel. diciembre de 2021;13(12):2461.
  68. Gao Z, Fan M, Das AT, Herrera-Carrillo E, Berkhout B. Extinction of all infectious HIV in cell culture by the CRISPR-Cas12a system with only a single crRNA. Nucleic Acids Res. 2020 Jun 4;48(10):5527-5539. doi: 10.1093/nar/gkaa226. PMID: 32282899; PMCID: PMC7261156.
  69. Sessions KJ, Chen YY, Hodge CA, Hudson TR, Eszterhas SK, Hayden MS, et al. Analysis of CRISPR/Cas9 Guide RNA Efficiency and Specificity Against Genetically Diverse HIV-1 Isolates. AIDS Res Hum Retroviruses. octubre de 2020;36(10):862-74.
  70. Liu Y, Binda CS, Berkhout B, Das AT. CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA. Journal of Virology. 20 de noviembre de 2023;97(12):e01334-23. Lin D, Scheller SH, Robinson MM, Izadpanah R, Alt EU, Braun SE. Increased Efficiency for Biallelic Mutations of the CCR5 Gene by CRISPR-Cas9 Using Multiple Guide RNAs As a Novel Therapeutic Lit Option for Human Immunodeficiency Virus. CRISPR J. febrero de 2021;4(1):92-103.
  71. Xu Y, Peng X, Zheng Y, Jin C, Lu X, Han D, et al. Inactivation of Latent HIV-1 Proviral DNA Using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Treatment and the Assessment of Off-Target Effects. Frontiers in Microbiology. 2021;12.
  72. Cardona ME, Hinkula J, Gustafsson K, Christensson B, Wahren B, Mohamed AJ, et al. Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev. Mol Biol Rep. noviembre de 2022;49(11):11187-92.
  73. Small RNAs to treat human immunodeficiency virus type 1 infection by gene therapy - ScienceDirect (Internet). (citado 17 de julio de 2023). Disponible en: https://www.sciencedirect.com/science/article/pii/S1879625719300069?via%3Dihub
  74. Cao S, Woodrow KA. Nanotechnology approaches to eradicating HIV reservoirs. European Journal of Pharmaceutics and Biopharmaceutics. 2019;138:48-63.
  75. Dong, W.; Kantor, B. Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas: Current State and Perspectives. Viruses 2021, 13, 1288.
  76. Marsden MD, Zack JA. HIV cure strategies: a complex approach for a complicated viral reservoir? Future Virology. enero de 2019;14(1):5-8.
  77. Sullivan NT, Allen AG, Atkins AJ, Chung CH, Dampier W, Nonnemacher MR, et al. Designing Safer CRISPR/Cas9 Therapeutics for HIV: Defining Factors That Regulate and Technologies Used to Detect Off-Target Editing. Front Microbiol. 12 de agosto de 2020;11:1872.
  78. Rothemejer FH, Lauritsen NP, Juhl AK, Schleimann MH, König S, Søgaard OS, et al. Development of HIV-Resistant CAR T Cells by CRISPR/Cas-Mediated CAR Integration into the CCR5 Locus. Viruses. 10 de enero de 2023;15(1):202.
  79. McLaurin KA, Li H, Khalili K, Mactutus CF, Booze RM. HIV-1 mRNA knockdown with CRISPR/CAS9 enhances neurocognitive function. J Neurovirol. 2024;30(1):71-85.

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