Aug 2026· Virologica Sinica· 0 citations· 306 references
Medicine
TL;DR
This review illustrates how HSV-1 has evolved from a naturally neurotropic virus into a versatile biomedical tool, whose therapeutic and research potential emerges from the precise matching of viral properties with disease-specific requirements, delivery contexts, and functional objectives.
Abstract
Herpes simplex virus type 1 (HSV-1) has emerged as a versatile platform for gene delivery, oncolytic immunotherapy, and neural circuit mapping. Its large genome, broad tropism, and engineering flexibility enable delivery of large or multi-component payloads that exceed the capacity of many conventional viral vectors. HSV-1-based vectors span a continuum of architectures, each representing a distinct design space shaped by trade-offs among replication competence, payload size, immune engagement, biosafety, and manufacturing robustness. Advances in bacterial artificial chromosome recombineering, CRISPR-based editing, and synthetic genome assembly, together with insights from structural and systemic biology, have accelerated the transition from empirical vector construction to more rational programmable genome design. These technologies enable modular control of viral entry, transcription, genome replication/maintenance, and host immune interactions. Clinical successes such as T-VEC, G47Δ, and B-VEC have validated the clinical potential of HSV-1 engineering, yet broader translation remains limited by antiviral immunity, inefficient delivery, epigenetic silencing, genome instability, and manufacturing challenges. In this review, we illustrate how HSV-1 has evolved from a naturally neurotropic virus into a versatile biomedical tool, whose therapeutic and research potential emerges from the precise matching of viral properties with disease-specific requirements, delivery contexts, and functional objectives.
This review provides a comprehensive overview of the current status of viral and non-viral vector systems for in vivo and ex vivo applications, and key comparisons are made across safety, efficacy, scalability, and immune responses.
This article aims to provide a working framework for verifying the potency, genomic integrity, and clinical safety of vector-based gene therapies—one intended to be useful both to laboratories developing these products and to those responsible for regulating them.
Yusra A. Radeef, Z. Abdullah, Eman Fadhel Abbas Awadh· International Journal of Mul...· 0 citations
This review comprehensively evaluates the rational design of classical animal herpesvirus vectors, including pseudorabies virus, herpesvirus of turkeys, and feline herpesvirus type 1, providing perspectives on how continuous biotechnological innovations will empower herpesvirus vectors to serve as formidable prophylactic tools against emerging and re-emerging infectious diseases.
Jiahui Guo, Chen Mei, Xinyao Sun et al.· Frontiers in Microbiology· 0 citations
Lentiviral vectors have revolutionized gene therapy by efficient and stable transduction of dividing and non-dividing cells, their large packaging capacity, and their compatibility with pseudotyping to alter viral tropism. The vesicular stomatitis virus glycoprotein (VSV-G) is widely used as a viral envelope protein of choice to pseudotype lentiviral vector particles as it confers exceptional particle stability and a broad tropism, due to the ubiquitous nature of the low-density lipoprotein receptor (LDLR). While this broad tropism facilitates transduction of diverse cell types, it precludes accurate in vivo targeting of specific cell populations. Structural insights into VSV-G have made receptor-blinding possible and revealed sites amenable to mutation while preserving fusion capacity. Coupled with targeting moieties, VSV-G pseudotyped lentiviral particles are redirected towards cells expressing target antigens. Such targeted vectors open new possibilities for in vivo gene therapy across oncology, infectious diseases, transplantation medicine, and other diseases. Use of targeted vectors will make in vivo gene therapy more accessible than cost-intensive ex vivo gene therapies. Since targeted vectors will be available as 'off-the-shelf' drugs, they will also drastically reduce time-to-treatment. This review highlights advances in bioengineering to exploit the versatility of VSV-G-pseudotyped lentiviral vectors and explores their vast potential for targeted gene delivery.
Anjali Shrivastava, Felix L. Warnecke, J. Schott et al.· Molecular Therapy· 0 citations
This review examines how biophysical properties of viral vectors, lipid nanoparticles, and hybrid virus-like particles influence editor delivery performance and explores how the notion of carrier systems shifts in diseased states like solid tumour cancers, autoimmune psoriasis of the skin, and the autosomal monogenic cystic fibrosis.
Upasana Ghosh, Andy Tay· Journal of Controlled Releas...· 0 citations
Immuno-oncology has reshaped the therapeutic landscape of cancer treatment by shifting focus from directly targeting tumor cells to mobilizing the immune system against malignancies. Among the most transformative advances in this field is the development of chimeric antigen receptor T-cell therapy, which has demonstrated remarkable efficacy in hematologic cancers. However, persistent challenges such as limited durability, immune escape, toxicity, and poor performance in solid tumors have constrained its broader clinical impact. The emergence of clustered regularly interspaced short palindromic repeats (CRISPR) genome editing has introduced a powerful and versatile platform for engineering immune cells with enhanced specificity, persistence, and functionality. CRISPR-based approaches enable precise gene knockout, targeted gene insertion, epigenetic modulation, and multiplex editing, allowing researchers to redesign immune cells at multiple regulatory levels. These capabilities have significantly advanced CAR-T cell engineering and have catalyzed the development of next-generation immune effectors, including natural killer cells, macrophages, and stem cell-derived immune populations. Furthermore, CRISPR technology has opened new avenues for overcoming the immunosuppressive tumor microenvironment, improving safety profiles, and enabling scalable, off-the-shelf therapies. This review provides a comprehensive examination of CRISPR applications in immuno-oncology, with an emphasis on CAR-T optimization and the engineering of next-generation immune cells. It discusses mechanistic foundations, technological innovations, preclinical and clinical advancements, safety considerations, and future directions. Collectively, CRISPR-driven immune engineering represents a paradigm shift toward more precise, effective, and accessible cancer immunotherapies.
Adewale Adeleke· International Journal for Sc...· 0 citations
