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.
Bo Yang, Zhi-Yu Liu, Feng Xiong et al.· Virologica Sinica· 0 citations
Adeno-associated viruses (AAVs) are widely used vectors for gene therapy owing to their nonpathogenic nature, low immunogenicity, and ability to support long-term transgene expression. However, the tissue tropism and immune response of AAVs are strongly dependent on their capsid serotype. Although hundreds of naturally occurring AAV variants have been isolated, many remain unvectorised and poorly characterized. Therefore, the discovery and development of previously uncharacterised native serotypes retain valuable. Here, we generated a novel recombinant AAV vector rAAV.hu.S17, derived from the human spleen isolate AAV.hu.S17, and systematically evaluated its capsid features, in vitro transduction, and in vivo tissue tropism. Sequence analysis showed that AAV.hu.S17 is closely related to AAV2 and AAV3, and shares 90.9% amino acid identity to AAV2 across the capsid proteins. High-titer vector production was achieved using the triple-plasmid system, with rAAV.hu.S17 yielding approximately 2.68-fold more vector than that of rAAV2. Although rAAV.hu.S17 showed ∼20-fold lower transduction in HEK293T cells than rAAV2 in vitro, it mediated higher neuronal transduction in the mouse primary visual cortex (V1) in vivo. Following intravitreal injection into C57BL/6 mice, rAAV.hu.S17 preferentially transduced photoreceptors in the outer nuclear layer (ONL), with minimal transduction of the inner nuclear layer (INL) and the ganglion cell layer (GCL). Collectively, these results demonstrate that rAAV.hu.S17 exhibits transduction characteristics distinct from those of rAAV2 in both the brain and retina. This study provides the first vectorization and biological characterization of the previously uncharacterized human AAV isolate AAV.hu.S17 and expands the repertoire of naturally occurring AAV capsids available for future biological investigation and vector engineering.
Wenyan Guo, Jiawen Sun, Fei Wang et al.· Journal of Genetic Engineeri...· 0 citations