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The review also covers broader gene-therapy concepts, including vaccine development, highlights COVID-19 adenovirus-based vaccine examples, summarizes preclinical proof-of-concept, reports clinical trial evidence for safety and efficacy, and notes approved viral-based drugs and 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Lundstrom, K. Viral Vectors  \nin Gene Therapy: Where Do We Stand in 2023? Viruses 2023, 15, 698 . [https://doi.org/10.3390/v15030698](https://doi.org/10.3390/v15030698)  \nAcademic Editors: Ottmar  \nHerchenröder and Brigitte Pützer  \nReceived: 18 January 2023  \nRevised: 23 February 2023  \nAccepted: 2 March 2023  \nPublished: 7 March 2023  \nCopyright: © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nPanTherapeutics, CH1095 Lutry, Switzerland; [lundstromkenneth@gmail.com](lundstromkenneth@gmail.com)  \nAbstract: Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing anti-tumor, toxic, suicide and immunostimulatory genes, such as cytokines and chemokines, have been applied. Oncolytic viruses, which specifically replicate in and kill tumor cells, have provided tumor eradication, and even cure of cancers in animal models. In a broader meaning, vaccine development against infectious diseases and various cancers has been considered as a type of gene therapy. Especially in the case of COVID-19 vaccines, adenovirus-based vaccines such as ChAdOx1 nCoV-19 and Ad26.COV2.Shave demonstrated excellent safety and vaccine efficacy in clinical trials, leading to Emergency Use Authorization in many countries. Viral vectors have shown great promise in the treatment of chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, hemophilia, 􀀌 -thalassemia, and sickle cell disease (SCD) . Proof-of-concept has been established in preclinical studies in various animal models. Clinical gene therapy trials have confirmed good safety, tolerability, and therapeutic efficacy. Viral-based drugs have been approved for cancer, hematological, metabolic, neurological, and ophthalmological diseases as well as for vaccines. For example, the adenovirusbased drug Gendicine® for non-small-cell lung cancer, the reovirus-based drug Reolysin® for ovarian cancer, the oncolytic HSV T-VEC for melanoma, lentivirus-based treatment of ADA-SCID disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease have been approved for human use.  \nKeywords: viral vector; gene therapy; cancer; chronic disease; vaccines; preclinical models; clinical trials; approved drugs  \n1. Introduction  \nGene therapy has been defined as the supplementation, correction, or modification of malfunctional genes by functional equivalents for therapeutic correction of the absence or reduced levels of gene expression activity [1] . A broader definition considersoligonucleotide- [2] and RNA interference (RNAi)-based gene silencing [3], immunotherapy, especially cancer immunotherapy, and vaccine development as gene therapy [4] . More recently, stem cell technologies [5], chimeric antigen receptor (CAR) T-cell therapy [6], and Clustered Regularly Interspaced Short Palindromic (CRISPR) [7], providing unprecedent possibilities for gene replacement and gene editing, have also received gene therapy status.  \nViral vectors have played a central role in gene therapy because of their superior gene delivery capacity compared to non-viral vectors. Moreover, the virus-based transgene expression, depending on the needs, for both short-term and long-term duration can be achieved. For example, for cancer gene therapy, short-term high-level transgene expression is advantageous, whereas for chronic diseases such as hemophilia, long-term transgene expression is necessary. However, the application of viral vectors requires a higher biosafety level compared to non-viral vectors due t","cbCais00QsBbNgkk","https://ap.wps.com/l/cbCais00QsBbNgkk","pdf",974102,35,"English","# Introduction\n# Viral Vector-Based Delivery","[{\"question\":\"What role do viral vectors play in gene therapy compared with non-viral vectors?\",\"answer\":\"Viral vectors are central because they deliver genes more effectively than non-viral vectors, enabling transgene expression for short or long durations depending on therapeutic needs.\"},{\"question\":\"How are viral vectors used for cancer gene therapy and tumor control?\",\"answer\":\"Cancer applications include vectors expressing anti-tumor, toxic, suicide, and immunostimulatory genes, and oncolytic viruses that selectively replicate in and kill tumor cells.\"},{\"question\":\"What evidence from clinical trials and approved products is highlighted?\",\"answer\":\"Clinical trials are described as confirming good safety, tolerability, and therapeutic efficacy, and the review lists viral-based drugs and vaccines approved for multiple disease areas, including cancers and Ebola vaccination.\"}]","Viral Vectors in Gene Therapy: Where Do We Stand in 2023? - Review | PDF",1790243037,88]