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: 15 nov. 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.
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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.
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