Gene therapy of neurological and non-neurological diseases using herpes simplex virus vectors
Main Article Content
Abstract
Two main types of vectors can be derived from herpes simplex type 1 (HSV-1), non-replicative vectors and replication-selective oncolytic vectors. The main goal of this review is to describe the key features that make non-replicative HSV-1 vectors (nrHSV-1) extremely appealing for gene therapy of peripheral and central nerve diseases. This includes the many outstanding adaptations that this human neurotropic virus has developed to safely infect, persist, and perform long-term gene expression in neurons, their very large transgene cargo capacity, unique amongst nuclear mammalian viruses, and the very important fact that they can be readministered several times due to the extremely low levels of immunological responses they elicit. This review also describes several preclinical studies as well as the clinical trials that have been developed or are ongoing with nrHSV-1, including gene therapy of cancer-related intractable pain and of recessive dystrophic epidermolysis bullosa (RDEB), which has been recently approved by the FDA. In the second part of this review, we compare side-by-side, the advantages and the drawbacks of nrHSV-1 and adeno-associated vectors (AAV), the most currently used gene therapy vector. Lastly, we will very briefly describe oncolytic vectors and a second type of nrHSV-1 vectors known as amplicons.
Keywords:
Gene therapy, Herpes simplex virus, Non-replicative vectors, Neurological diseases, Transgene cargo, Adeno-associated vectors, Oncolytic vectors
Article Details
How to Cite
JOUSSAIN, Charles; EPSTEIN, Alberto L..
Gene therapy of neurological and non-neurological diseases using herpes simplex virus vectors.
Medical Research Archives, [S.l.], v. 12, n. 7, july 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5659>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i7.5659.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. James, C. et al. (2020) Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ 98, 315-329. 10.2471/blt.19.237149
2. Knipe, D. et al. (2021) Herpes simplex viruses: Mechanisms of lytic and latent infection. In Fields Virology (7th edn) (Howley, P.M. et al., eds), pp. 235-296, Wolters Kluwer
3. Whitley, R. and Baines, J. (2018) Clinical management of herpes simplex virus infections: past, present, and future. F1000Research 7. 10.12688/f1000research.16157.1
4. Zhu, H. and Zheng, C. (2020) The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1. Microbiol Mol Biol Rev 84. 10.1128/mmbr.00099-20
5. Pinninti, S.G. and Kimberlin, D.W. (2018) Neonatal herpes simplex virus infections. Semin Perinatol 42, 168-175. 10.1053/j.semperi.2018.02.004
6. Danastas, K. et al. (2020) Herpes Simplex Virus Type 1 Interactions with the Interferon System. International journal of molecular sciences 21. 10.3390/ijms21145150
7. Skouboe, M.K. et al. (2023) Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System. Pathogens 12. 10.3390/pathogens12020310
8. Goss, J.R. et al. (2002) Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Diabetes 51, 2227-2232. 10.2337/diabetes.51.7.2227
9. Chahlavi, A. et al. (1999) Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice. Gene Ther 6, 1751-1758
10. Madavaraju, K. et al. (2020) Herpes Simplex Virus Cell Entry Mechanisms: An Update. Front Cell Infect Microbiol 10, 617578. 10.3389/fcimb.2020. 617578
11. Jambunathan, N. et al. (2021) Two Sides to Every Story: Herpes Simplex Type-1 Viral Glycoproteins gB, gD, gH/gL, gK, and Cellular Receptors Function as Key Players in Membrane Fusion. Viruses 13. 10.3390/v13091849
12. Smith, G.A. (2021) Navigating the Cytoplasm: Delivery of the Alphaherpesvirus Genome to the Nucleus. Curr Issues Mol Biol 41, 171-220. 10.21775/cimb.041.171
13. Bauer, D. and Tampe, R. (2002) Herpes viral proteins blocking the transporter associated with antigen processing TAP--from genes to function and structure. Curr Top Microbiol Immunol 269, 87-99.
14. Cohen, J.I. (2020) Herpesvirus latency. J Clin Invest 130, 3361-3369. 10.1172/jci136225
15. Artusi, S. et al. (2018) Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System. Diseases (Basel, Switzerland) 6. 10.3390/ diseases6030074
16. Aldrak, N. et al. (2021) Oncolytic Herpes Simplex Virus-Based Therapies for Cancer. Cells 10. 10.3390/cells10061541.
17. Krisky, D.M. et al. (1998) Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther 5, 1593-1603. 10.1038/sj.gt.3300766
18. Miyagawa, Y. et al. (2015) Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity. Proc Natl Acad Sci U S A 112, E1632-1641. 10.1073/pnas. 1423556112
19. Verlengia, G. et al. (2017) Engineered HSV vector achieves safe long-term transgene expression in the central nervous system. Sci Rep 7, 1507. 10.1038/s41598-017-01635-1.
20. Richart SM, Simpson SA, Krummenacher C, Whitbeck JC, Pizer LI, Cohen GH, Eisenberg RJ, Wilcox CL. Entry of herpes simplex virus type 1 into primary sensory neurons in vitro is mediated by Nectin-1/HveC. J Virol. 2003 Mar;77(5):3307-11. doi: 10.1128/jvi.77.5.3307-3311.2003. PMID: 12584355; PMCID: PMC149788.
21. Miranda-Saksena M, Denes CE, Diefenbach RJ, Cunningham AL. Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the Cytoskeleton. Viruses. 2018 Feb 23;10(2):92. doi: 10.3390/v10020092. PMID: 29473915; PMCID: PMC5850399.
22. Kurt-Jones EA, Orzalli MH, Knipe DM. Innate Immune Mechanisms and Herpes Simplex Virus Infection and Disease. Adv Anat Embryol Cell Biol. 2017;223:49-75. doi: 10.1007/978-3-319-53168-7_3. PMID: 28528439; PMCID: PMC7254490.
23. Cohen JI. Herpesvirus latency. J Clin Invest. 2020 Jul 1;130(7):3361-3369. doi: 10.1172/JCI 136225. PMID: 32364538; PMCID: PMC7324166.
24. Nicoll MP, Proença JT, Efstathiou S. The molecular basis of herpes simplex virus latency. FEMS Microbiol Rev. 2012 May;36(3):684-705. doi: 10.1111/j.1574-6976.2011.00320.x. Epub 2012 Jan 10. PMID: 22150699; PMCID: PMC3492847.
25. Bloom DC, Giordani NV, Kwiatkowski DL. Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta. 2010 Mar-Apr;1799(3-4):246-56. doi: 10.1016/j.bbagrm.2009 .12.001. Epub 2010 Jan 4. PMID: 20045093; PMCID: PMC2838971.
26. Lachmann R. Herpes simplex virus-based vectors. Int J Exp Pathol. 2004 Oct;85(4):177-90. doi: 10.1111/j.0959-9673.2004.00383.x. PMID: 15312123; PMCID: PMC2517519.
27. Chew T, Taylor KE, Mossman KL. Innate and adaptive immune responses to herpes simplex virus. Viruses. 2009 Dec;1(3):979-1002. doi: 10.3390/v1030979. Epub 2009 Nov 18. PMID: 21994578; PMCID: PMC3185534.
28. Miyazato M, Sugaya K, Goins WF, Wolfe D, Goss JR, Chancellor MB, de Groat WC, Glorioso JC, Yoshimura N. Herpes simplex virus vector-mediated gene delivery of glutamic acid decarboxylase reduces detrusor overactivity in spinal cord-injured rats. Gene Ther. 2009 May; 16(5):660-8. doi: 10.1038/gt.2009.5. Epub 2009 Feb 19. PMID: 19225548; PMCID: PMC2881227.
29. Jia C, Yoshimura N, Liao L. Herpes simplex virus vector-mediated gene transfer of kynurenine aminotransferase improves detrusor overactivity in spinal cord-injured rats. Gene Ther. 2014 May;21 (5):484-9. doi: 10.1038/gt.2014.19. Epub 2014 Mar 6. PMID: 24598891.
30. Goss JR, Mata M, Goins WF, Wu HH, Glorioso JC, Fink DJ. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther. 2001 Apr;8(7):551-6. doi: 10.1038/ sj.gt.3301430. PMID: 11319622.
31. Chattopadhyay M, Zhou Z, Hao S, Mata M, Fink DJ. Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy. Mol Pain. 2012 Mar 22;8:17. doi: 10. 1186/1744-8069-8-17. PMID: 22439790; PMCID: PMC3388457.
32. Walwyn WM, Matsuka Y, Arai D, Bloom DC, Lam H, Tran C, Spigelman I, Maidment NT. HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy. Exp Neurol. 2006 Mar;198(1):260-70. doi: 10.1016/ j.expneurol.2005.12.006. Epub 2006 Jan 20. PMID: 16427624.
33. Chattopadhyay M, Mata M, Goss J, Wolfe D, Huang S, Glorioso JC, Fink DJ. Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes simplex virus-mediated gene transfer. Diabetologia. 2007 Jul;50(7):1550-8. doi: 10.1007/s00125-007-0702-4. Epub 2007 May 17. PMID: 17508196.
34. Fink D. J., Wechuck, J., Mata, M. & Glorioso J.C. Gene therapy for pain: results of a phase I clinical trial. Ann. Neurol. 70, 207–212 (2011).
35. Gurevich, I. et al. (2022) In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med 28, 780-788. 10.1038/s41591-022-01737-y
36. Guide, S.V. et al. (2022) Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med 387, 2211-2219. 10.1056 /NEJMoa2206663
37. Bauer, D. and Tampe, R. (2002) Herpes viral proteins blocking the transporter associated with antigen processing TAP--from genes to function and structure. Curr Top Microbiol Immunol 269, 87-99.
38. Dhillon, S. (2023) Beremagene Geperpavec: First Approval. Drugs. 10.1007/s40265-023-01921-5
39. De Rosa, L. and De Luca, M. (2022) The joint battle to tackle epidermolysis bullosa through gene therapy. Trends Mol Med 28, 533-535. 10.1016/j.molmed.2022.05.001
40. Freedman, J.C. et al. (2021) Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis. J Invest Dermatol 141, 874-882.e876. 10.1016/j.jid.2020.07.035
41. Wang, JH., Gessler, D.J., Zhan, W. et al. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig Transduct Target Ther 9, 78 (2024). https://doi.org/10.1038/s41392-024-01780-w
42. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14. Erratum in: Lancet. 2017 Aug 26;390(1 0097):848. PMID: 28712537; PMCID: PMC5726391.
43. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198. PMID: 29091557.
44. Im DS, Muzyczka N. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell. 1990 May 4;61(3):447-57. doi: 10.1016/0092-8674( 90)90526-k. PMID: 2159383.
45. Rosas LE, Grieves JL, Zaraspe K, La Perle KM, Fu H, McCarty DM. Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity. Mol Ther. 2012 Nov;20(11):2098-110. doi: 10.1038/mt.2012.197. Epub 2012 Sep 18. PMID: 22990674; PMCID: PMC3498805.
46. Martins KM, Breton C, Zheng Q, Zhang Z, Latshaw C, Greig JA, Wilson JM. Prevalent and Disseminated Recombinant and Wild-Type Adeno-Associated Virus Integration in Macaques and Humans. Hum Gene Ther. 2023 Nov;34(21-22):108 1-1094. doi: 10.1089/hum.2023.134. Epub 2023 Nov 6. PMID: 37930949; PMCID: PMC10659022.
47. Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G, et al. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet. 2015 Oct;47(10):1187-93. doi: 10.1038/ng.3389. Epub 2015 Aug 24. PMID: 26301494.
48. Greig, J.A., Martins, K.M., Breton, C. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01974-7
49. Lilley CE, Groutsi F, Han Z, Palmer JA, Anderson PN, Latchman DS, Coffin RS. Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene delivery to the central nervous system in vivo. J Virol. 2001 May;75(9):4343-56. doi: 10.1128/JVI.75.9.4343-43 56.2001. PMID: 11287583; PMCID: PMC114179.
50. Gimenez-Cassina A, Wade-Martins R, Gomez-Sebastian S, Corona JC, Lim F, Diaz-Nido J. Infectious delivery and long-term persistence of transgene expression in the brain by a 135-kb iBAC-FXN genomic DNA expression vector. Gene Ther. 2011 Oct;18(10):1015-9. doi: 10.1038/gt.201 1.45. Epub 2011 Apr 14. PMID: 21490681.
51. Zhu J, Kang W, Wolfe JH, Fraser NW. Significantly increased expression of beta-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector. Mol Ther. 2000 Jul;2(1):82-94. doi: 10.1006/mthe .2000.0093. PMID: 10899831.
52. Zsebo K, Yaroshinsky A, Rudy JJ, Wagner K, ET AL. Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res. 2014 Jan 3;114(1):101-8. doi: 10.1161/CIRCRESAHA.113.302421. Epub 2013 Sep 24. PMID: 24065463.
53. Wang Z, Ma HI, Li J, Sun L, Zhang J, Xiao X. Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo. Gene Ther. 2003 Dec;10(26):2105-11. doi: 10.1038/sj.gt.3302133. PMID: 14625564.
54. Recillas-Targa F, Valadez-Graham V, Farrell CM. Prospects and implications of using chromatin insulators in gene therapy and transgenesis. Bioessays. 2004 Jul;26(7):796-807. doi: 10.1002/bi es.20059. PMID: 15221861.
55. Gross DA, Tedesco N, Leborgne C, Ronzitti G. Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients. Front Immunol. 2022 Apr 7;13:857276. doi: 10.338 9/fimmu.2022.857276. PMID: 35464422; PMCID: PMC9022790.
56. Philippidis A. Fourth Boy Dies in Clinical Trial of Astellas' AT132. Hum Gene Ther. 2021 Oct;32(19-20):1008-1010. doi: 10.1089/hum.2021. 29182.bfs. PMID: 34662231.
57. Philippidis A. Novartis Confirms Deaths of Two Patients Treated with Gene Therapy Zolgensma. Hum Gene Ther. 2022 Sep;33(17-18):842-844. doi: 10.1089/hum.2022.29216.bfs. PMID: 36125439.
58. Guillou J, de Pellegars A, Porcheret F, Frémeaux-Bacchi V, et al. Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy. Blood Adv. 2022 Jul 26;6(14):4266-4270. doi: 10.1182/bloodadvances. 2021006419. PMID: 35584395; PMCID: PMC9327533.
59. Lek A, Wong B, Keeler A, Blackwood M, Ma K, Huang S, et al. Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy. N Engl J Med. 2023 Sep 28;389(13): 1203-1210. doi: 10.1056/NEJMoa2307798. PMID: 37754285.
60. Kishimoto TK, Samulski RJ. Addressing high dose AAV toxicity - 'one and done' or 'slower and lower'? Expert Opin Biol Ther. 2022 Sep;22(9):106 7-1071. doi: 10.1080/14712598.2022.2060737. Epub 2022 Apr 3. PMID: 35373689.
61. High-dose AAV gene therapy deaths. Nat Biotechnol 38, 910 (2020). https://doi.org/10.1038/s41587-020-0642-9
62. Stone, D., Aubert, M. & Jerome, K.R. Adeno-associated virus vectors and neurotoxicity—lessons from preclinical and human studies. Gene Ther (2023). https://doi.org/10.1038/s41434-023-00405-1
63. Han, F. et al. (2018) Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex Virus Vectors in the Absence of Immediate Early Gene Expression. J Virol 92. 10.1128/jvi.00536-18.
64. Epstein AL. HSV-1-derived amplicon vectors: Recent technological improvements and remaining difficulties – A review. Mem Inst Oswaldo Cruz. 2009;104(3):399-410.
65 Saeki Y, Fraefel C, Ichikawa T, Breakefield XO, Chiocca E.A. Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. Mol Ther. 2001 3: 591-601.
66. Zaupa, C.; Revol-Guyot, V.; Epstein, A.L. Improved packaging system for generation of high levels non-cytotoxic HSV-1 amplicon vectors using Cre-loxP site-specific recombination to delete the packaging signals of defective helper genomes. Hum Gene Ther. 2003, 14, 1049-1063.
67. Xiong, F., Yang, H., Song, YG. et al. An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing. Nat Commun 13, 7645 (2022). https://doi.org/10.1038/s41467-022-35355-6
68. Joussain C, Le Coz O, Pichugin A, Marconi P, Lim F, Sicurella M, Salonia A, Montorsi F, Wandosell F, Foster K, Giuliano F, Epstein AL, Aranda Muñoz A. Botulinum Neurotoxin Light Chains Expressed by Defective Herpes Simplex Virus Type-1 Vectors Cleave SNARE Proteins and Inhibit CGRP Release in Rat Sensory Neurons. Toxins (Basel). 2019 Feb 19;11(2):123. doi: 10.3390/toxins11020123.
69. Joussain C, Le Coz O, Pichugin A, Marconi P, Lim F, Sicurella M, Foster K, Giuliano F, Epstein AL, Aranda Muñoz A. Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters. Int J Mol Sci. 2022 Jul 30;23(15):8474. doi: 10.3390/ijms23158474.
70. Soukupová M, Zucchini S, Trempat P, Ingusci S, Perrier-Biollay C, Barbieri M, Cattaneo S, Bettegazzi B, Falzoni S, Berthommé H, Simonato M. Improvement of HSV-1 based amplicon vectors for a safe and long-lasting gene therapy in non-replicating cells. Mol Ther Methods Clin Dev. 2021 Mar 29;21:399-412. doi: 10.1016/j.omtm.2021.03.020.
71. Ho, I., Miao, L., Sia, K. et al. Targeting human glioma cells using HSV-1 amplicon peptide display vector. Gene Ther 17, 250–260 (2010). https://doi.org/10.1038/gt.2009.128
72. Peters, C. and Rabkin, S.D. (2015) Designing Herpes Viruses as Oncolytics. Mol Ther Oncolytics 2, 15010. 10.1038/mto.2015.10
73. Zhang, S. and Rabkin, S.D. (2021) The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy? Expert Opin Drug Discov 16, 391-410. 10.1080/ 17460441.2021.1850689
74. Bommareddy, P.K. et al. (2018) Oncolytic Herpes Simplex Viruses as a Paradigm for the Treatment of Cancer. Annual Review of Cancer Biology 2, 155-173. 10.1146/annurev-cancerbio-030617-050254
75. Aldrak, N. et al. (2021) Oncolytic Herpes Simplex Virus-Based Therapies for Cancer. Cells 10. 10.3390/cells10061541
76. Jahan, N. et al. (2021) In Situ Cancer Vaccination and Immunovirotherapy Using Oncolytic HSV. Viruses 13. 10.3390/v13091740.
77. Koch, M.S. et al. (2020) HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers (Basel) 12. 10.3390 /cancers12123514
78. Todo, T. et al. (2022) Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nat Med. 10.1038/s41591-022-01897-x
79. Scanlan, H. et al. (2022) Herpes simplex virus 1 as an oncolytic viral therapy for refractory cancers. Front Oncol 12, 940019. 10.3389/fonc.2022.940019
2. Knipe, D. et al. (2021) Herpes simplex viruses: Mechanisms of lytic and latent infection. In Fields Virology (7th edn) (Howley, P.M. et al., eds), pp. 235-296, Wolters Kluwer
3. Whitley, R. and Baines, J. (2018) Clinical management of herpes simplex virus infections: past, present, and future. F1000Research 7. 10.12688/f1000research.16157.1
4. Zhu, H. and Zheng, C. (2020) The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1. Microbiol Mol Biol Rev 84. 10.1128/mmbr.00099-20
5. Pinninti, S.G. and Kimberlin, D.W. (2018) Neonatal herpes simplex virus infections. Semin Perinatol 42, 168-175. 10.1053/j.semperi.2018.02.004
6. Danastas, K. et al. (2020) Herpes Simplex Virus Type 1 Interactions with the Interferon System. International journal of molecular sciences 21. 10.3390/ijms21145150
7. Skouboe, M.K. et al. (2023) Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System. Pathogens 12. 10.3390/pathogens12020310
8. Goss, J.R. et al. (2002) Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Diabetes 51, 2227-2232. 10.2337/diabetes.51.7.2227
9. Chahlavi, A. et al. (1999) Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice. Gene Ther 6, 1751-1758
10. Madavaraju, K. et al. (2020) Herpes Simplex Virus Cell Entry Mechanisms: An Update. Front Cell Infect Microbiol 10, 617578. 10.3389/fcimb.2020. 617578
11. Jambunathan, N. et al. (2021) Two Sides to Every Story: Herpes Simplex Type-1 Viral Glycoproteins gB, gD, gH/gL, gK, and Cellular Receptors Function as Key Players in Membrane Fusion. Viruses 13. 10.3390/v13091849
12. Smith, G.A. (2021) Navigating the Cytoplasm: Delivery of the Alphaherpesvirus Genome to the Nucleus. Curr Issues Mol Biol 41, 171-220. 10.21775/cimb.041.171
13. Bauer, D. and Tampe, R. (2002) Herpes viral proteins blocking the transporter associated with antigen processing TAP--from genes to function and structure. Curr Top Microbiol Immunol 269, 87-99.
14. Cohen, J.I. (2020) Herpesvirus latency. J Clin Invest 130, 3361-3369. 10.1172/jci136225
15. Artusi, S. et al. (2018) Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System. Diseases (Basel, Switzerland) 6. 10.3390/ diseases6030074
16. Aldrak, N. et al. (2021) Oncolytic Herpes Simplex Virus-Based Therapies for Cancer. Cells 10. 10.3390/cells10061541.
17. Krisky, D.M. et al. (1998) Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther 5, 1593-1603. 10.1038/sj.gt.3300766
18. Miyagawa, Y. et al. (2015) Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity. Proc Natl Acad Sci U S A 112, E1632-1641. 10.1073/pnas. 1423556112
19. Verlengia, G. et al. (2017) Engineered HSV vector achieves safe long-term transgene expression in the central nervous system. Sci Rep 7, 1507. 10.1038/s41598-017-01635-1.
20. Richart SM, Simpson SA, Krummenacher C, Whitbeck JC, Pizer LI, Cohen GH, Eisenberg RJ, Wilcox CL. Entry of herpes simplex virus type 1 into primary sensory neurons in vitro is mediated by Nectin-1/HveC. J Virol. 2003 Mar;77(5):3307-11. doi: 10.1128/jvi.77.5.3307-3311.2003. PMID: 12584355; PMCID: PMC149788.
21. Miranda-Saksena M, Denes CE, Diefenbach RJ, Cunningham AL. Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the Cytoskeleton. Viruses. 2018 Feb 23;10(2):92. doi: 10.3390/v10020092. PMID: 29473915; PMCID: PMC5850399.
22. Kurt-Jones EA, Orzalli MH, Knipe DM. Innate Immune Mechanisms and Herpes Simplex Virus Infection and Disease. Adv Anat Embryol Cell Biol. 2017;223:49-75. doi: 10.1007/978-3-319-53168-7_3. PMID: 28528439; PMCID: PMC7254490.
23. Cohen JI. Herpesvirus latency. J Clin Invest. 2020 Jul 1;130(7):3361-3369. doi: 10.1172/JCI 136225. PMID: 32364538; PMCID: PMC7324166.
24. Nicoll MP, Proença JT, Efstathiou S. The molecular basis of herpes simplex virus latency. FEMS Microbiol Rev. 2012 May;36(3):684-705. doi: 10.1111/j.1574-6976.2011.00320.x. Epub 2012 Jan 10. PMID: 22150699; PMCID: PMC3492847.
25. Bloom DC, Giordani NV, Kwiatkowski DL. Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta. 2010 Mar-Apr;1799(3-4):246-56. doi: 10.1016/j.bbagrm.2009 .12.001. Epub 2010 Jan 4. PMID: 20045093; PMCID: PMC2838971.
26. Lachmann R. Herpes simplex virus-based vectors. Int J Exp Pathol. 2004 Oct;85(4):177-90. doi: 10.1111/j.0959-9673.2004.00383.x. PMID: 15312123; PMCID: PMC2517519.
27. Chew T, Taylor KE, Mossman KL. Innate and adaptive immune responses to herpes simplex virus. Viruses. 2009 Dec;1(3):979-1002. doi: 10.3390/v1030979. Epub 2009 Nov 18. PMID: 21994578; PMCID: PMC3185534.
28. Miyazato M, Sugaya K, Goins WF, Wolfe D, Goss JR, Chancellor MB, de Groat WC, Glorioso JC, Yoshimura N. Herpes simplex virus vector-mediated gene delivery of glutamic acid decarboxylase reduces detrusor overactivity in spinal cord-injured rats. Gene Ther. 2009 May; 16(5):660-8. doi: 10.1038/gt.2009.5. Epub 2009 Feb 19. PMID: 19225548; PMCID: PMC2881227.
29. Jia C, Yoshimura N, Liao L. Herpes simplex virus vector-mediated gene transfer of kynurenine aminotransferase improves detrusor overactivity in spinal cord-injured rats. Gene Ther. 2014 May;21 (5):484-9. doi: 10.1038/gt.2014.19. Epub 2014 Mar 6. PMID: 24598891.
30. Goss JR, Mata M, Goins WF, Wu HH, Glorioso JC, Fink DJ. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther. 2001 Apr;8(7):551-6. doi: 10.1038/ sj.gt.3301430. PMID: 11319622.
31. Chattopadhyay M, Zhou Z, Hao S, Mata M, Fink DJ. Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy. Mol Pain. 2012 Mar 22;8:17. doi: 10. 1186/1744-8069-8-17. PMID: 22439790; PMCID: PMC3388457.
32. Walwyn WM, Matsuka Y, Arai D, Bloom DC, Lam H, Tran C, Spigelman I, Maidment NT. HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy. Exp Neurol. 2006 Mar;198(1):260-70. doi: 10.1016/ j.expneurol.2005.12.006. Epub 2006 Jan 20. PMID: 16427624.
33. Chattopadhyay M, Mata M, Goss J, Wolfe D, Huang S, Glorioso JC, Fink DJ. Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes simplex virus-mediated gene transfer. Diabetologia. 2007 Jul;50(7):1550-8. doi: 10.1007/s00125-007-0702-4. Epub 2007 May 17. PMID: 17508196.
34. Fink D. J., Wechuck, J., Mata, M. & Glorioso J.C. Gene therapy for pain: results of a phase I clinical trial. Ann. Neurol. 70, 207–212 (2011).
35. Gurevich, I. et al. (2022) In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med 28, 780-788. 10.1038/s41591-022-01737-y
36. Guide, S.V. et al. (2022) Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med 387, 2211-2219. 10.1056 /NEJMoa2206663
37. Bauer, D. and Tampe, R. (2002) Herpes viral proteins blocking the transporter associated with antigen processing TAP--from genes to function and structure. Curr Top Microbiol Immunol 269, 87-99.
38. Dhillon, S. (2023) Beremagene Geperpavec: First Approval. Drugs. 10.1007/s40265-023-01921-5
39. De Rosa, L. and De Luca, M. (2022) The joint battle to tackle epidermolysis bullosa through gene therapy. Trends Mol Med 28, 533-535. 10.1016/j.molmed.2022.05.001
40. Freedman, J.C. et al. (2021) Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis. J Invest Dermatol 141, 874-882.e876. 10.1016/j.jid.2020.07.035
41. Wang, JH., Gessler, D.J., Zhan, W. et al. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig Transduct Target Ther 9, 78 (2024). https://doi.org/10.1038/s41392-024-01780-w
42. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14. Erratum in: Lancet. 2017 Aug 26;390(1 0097):848. PMID: 28712537; PMCID: PMC5726391.
43. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198. PMID: 29091557.
44. Im DS, Muzyczka N. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell. 1990 May 4;61(3):447-57. doi: 10.1016/0092-8674( 90)90526-k. PMID: 2159383.
45. Rosas LE, Grieves JL, Zaraspe K, La Perle KM, Fu H, McCarty DM. Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity. Mol Ther. 2012 Nov;20(11):2098-110. doi: 10.1038/mt.2012.197. Epub 2012 Sep 18. PMID: 22990674; PMCID: PMC3498805.
46. Martins KM, Breton C, Zheng Q, Zhang Z, Latshaw C, Greig JA, Wilson JM. Prevalent and Disseminated Recombinant and Wild-Type Adeno-Associated Virus Integration in Macaques and Humans. Hum Gene Ther. 2023 Nov;34(21-22):108 1-1094. doi: 10.1089/hum.2023.134. Epub 2023 Nov 6. PMID: 37930949; PMCID: PMC10659022.
47. Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G, et al. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet. 2015 Oct;47(10):1187-93. doi: 10.1038/ng.3389. Epub 2015 Aug 24. PMID: 26301494.
48. Greig, J.A., Martins, K.M., Breton, C. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01974-7
49. Lilley CE, Groutsi F, Han Z, Palmer JA, Anderson PN, Latchman DS, Coffin RS. Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene delivery to the central nervous system in vivo. J Virol. 2001 May;75(9):4343-56. doi: 10.1128/JVI.75.9.4343-43 56.2001. PMID: 11287583; PMCID: PMC114179.
50. Gimenez-Cassina A, Wade-Martins R, Gomez-Sebastian S, Corona JC, Lim F, Diaz-Nido J. Infectious delivery and long-term persistence of transgene expression in the brain by a 135-kb iBAC-FXN genomic DNA expression vector. Gene Ther. 2011 Oct;18(10):1015-9. doi: 10.1038/gt.201 1.45. Epub 2011 Apr 14. PMID: 21490681.
51. Zhu J, Kang W, Wolfe JH, Fraser NW. Significantly increased expression of beta-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector. Mol Ther. 2000 Jul;2(1):82-94. doi: 10.1006/mthe .2000.0093. PMID: 10899831.
52. Zsebo K, Yaroshinsky A, Rudy JJ, Wagner K, ET AL. Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res. 2014 Jan 3;114(1):101-8. doi: 10.1161/CIRCRESAHA.113.302421. Epub 2013 Sep 24. PMID: 24065463.
53. Wang Z, Ma HI, Li J, Sun L, Zhang J, Xiao X. Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo. Gene Ther. 2003 Dec;10(26):2105-11. doi: 10.1038/sj.gt.3302133. PMID: 14625564.
54. Recillas-Targa F, Valadez-Graham V, Farrell CM. Prospects and implications of using chromatin insulators in gene therapy and transgenesis. Bioessays. 2004 Jul;26(7):796-807. doi: 10.1002/bi es.20059. PMID: 15221861.
55. Gross DA, Tedesco N, Leborgne C, Ronzitti G. Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients. Front Immunol. 2022 Apr 7;13:857276. doi: 10.338 9/fimmu.2022.857276. PMID: 35464422; PMCID: PMC9022790.
56. Philippidis A. Fourth Boy Dies in Clinical Trial of Astellas' AT132. Hum Gene Ther. 2021 Oct;32(19-20):1008-1010. doi: 10.1089/hum.2021. 29182.bfs. PMID: 34662231.
57. Philippidis A. Novartis Confirms Deaths of Two Patients Treated with Gene Therapy Zolgensma. Hum Gene Ther. 2022 Sep;33(17-18):842-844. doi: 10.1089/hum.2022.29216.bfs. PMID: 36125439.
58. Guillou J, de Pellegars A, Porcheret F, Frémeaux-Bacchi V, et al. Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy. Blood Adv. 2022 Jul 26;6(14):4266-4270. doi: 10.1182/bloodadvances. 2021006419. PMID: 35584395; PMCID: PMC9327533.
59. Lek A, Wong B, Keeler A, Blackwood M, Ma K, Huang S, et al. Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy. N Engl J Med. 2023 Sep 28;389(13): 1203-1210. doi: 10.1056/NEJMoa2307798. PMID: 37754285.
60. Kishimoto TK, Samulski RJ. Addressing high dose AAV toxicity - 'one and done' or 'slower and lower'? Expert Opin Biol Ther. 2022 Sep;22(9):106 7-1071. doi: 10.1080/14712598.2022.2060737. Epub 2022 Apr 3. PMID: 35373689.
61. High-dose AAV gene therapy deaths. Nat Biotechnol 38, 910 (2020). https://doi.org/10.1038/s41587-020-0642-9
62. Stone, D., Aubert, M. & Jerome, K.R. Adeno-associated virus vectors and neurotoxicity—lessons from preclinical and human studies. Gene Ther (2023). https://doi.org/10.1038/s41434-023-00405-1
63. Han, F. et al. (2018) Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex Virus Vectors in the Absence of Immediate Early Gene Expression. J Virol 92. 10.1128/jvi.00536-18.
64. Epstein AL. HSV-1-derived amplicon vectors: Recent technological improvements and remaining difficulties – A review. Mem Inst Oswaldo Cruz. 2009;104(3):399-410.
65 Saeki Y, Fraefel C, Ichikawa T, Breakefield XO, Chiocca E.A. Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome. Mol Ther. 2001 3: 591-601.
66. Zaupa, C.; Revol-Guyot, V.; Epstein, A.L. Improved packaging system for generation of high levels non-cytotoxic HSV-1 amplicon vectors using Cre-loxP site-specific recombination to delete the packaging signals of defective helper genomes. Hum Gene Ther. 2003, 14, 1049-1063.
67. Xiong, F., Yang, H., Song, YG. et al. An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing. Nat Commun 13, 7645 (2022). https://doi.org/10.1038/s41467-022-35355-6
68. Joussain C, Le Coz O, Pichugin A, Marconi P, Lim F, Sicurella M, Salonia A, Montorsi F, Wandosell F, Foster K, Giuliano F, Epstein AL, Aranda Muñoz A. Botulinum Neurotoxin Light Chains Expressed by Defective Herpes Simplex Virus Type-1 Vectors Cleave SNARE Proteins and Inhibit CGRP Release in Rat Sensory Neurons. Toxins (Basel). 2019 Feb 19;11(2):123. doi: 10.3390/toxins11020123.
69. Joussain C, Le Coz O, Pichugin A, Marconi P, Lim F, Sicurella M, Foster K, Giuliano F, Epstein AL, Aranda Muñoz A. Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters. Int J Mol Sci. 2022 Jul 30;23(15):8474. doi: 10.3390/ijms23158474.
70. Soukupová M, Zucchini S, Trempat P, Ingusci S, Perrier-Biollay C, Barbieri M, Cattaneo S, Bettegazzi B, Falzoni S, Berthommé H, Simonato M. Improvement of HSV-1 based amplicon vectors for a safe and long-lasting gene therapy in non-replicating cells. Mol Ther Methods Clin Dev. 2021 Mar 29;21:399-412. doi: 10.1016/j.omtm.2021.03.020.
71. Ho, I., Miao, L., Sia, K. et al. Targeting human glioma cells using HSV-1 amplicon peptide display vector. Gene Ther 17, 250–260 (2010). https://doi.org/10.1038/gt.2009.128
72. Peters, C. and Rabkin, S.D. (2015) Designing Herpes Viruses as Oncolytics. Mol Ther Oncolytics 2, 15010. 10.1038/mto.2015.10
73. Zhang, S. and Rabkin, S.D. (2021) The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy? Expert Opin Drug Discov 16, 391-410. 10.1080/ 17460441.2021.1850689
74. Bommareddy, P.K. et al. (2018) Oncolytic Herpes Simplex Viruses as a Paradigm for the Treatment of Cancer. Annual Review of Cancer Biology 2, 155-173. 10.1146/annurev-cancerbio-030617-050254
75. Aldrak, N. et al. (2021) Oncolytic Herpes Simplex Virus-Based Therapies for Cancer. Cells 10. 10.3390/cells10061541
76. Jahan, N. et al. (2021) In Situ Cancer Vaccination and Immunovirotherapy Using Oncolytic HSV. Viruses 13. 10.3390/v13091740.
77. Koch, M.S. et al. (2020) HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers (Basel) 12. 10.3390 /cancers12123514
78. Todo, T. et al. (2022) Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nat Med. 10.1038/s41591-022-01897-x
79. Scanlan, H. et al. (2022) Herpes simplex virus 1 as an oncolytic viral therapy for refractory cancers. Front Oncol 12, 940019. 10.3389/fonc.2022.940019