Shen Yangkun, Zhang Hucheng, Xue Mengzhou, Zheng Chunfu, Chen Qi
Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China.
Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Trends Pharmacol Sci. 2025 Apr;46(4):324-336. doi: 10.1016/j.tips.2025.02.006. Epub 2025 Mar 10.
Herpes simplex virus type 1 (HSV-1) is a DNA virus with strong replication capabilities, a large genomic payload (≥30 kb), and low toxicity, making it a prominent vector in cancer gene therapy. Clinically approved oncolytic HSV-1 (oHSV-1) variants, such as T-VEC and G47Δ, demonstrate safety and efficacy in localized tumors, but face challenges in treating metastatic disease. To address this issue, next-generation oHSV-1 designs focus on precision targeting and immune remodeling through the delivery of multiple exogenous genes. In this review, we provide an overview of the inherent characteristics of oHSV-1 as a gene delivery platform, focusing on its genetic modification strategies, safety challenges in clinical applications, and future directions to maximize its therapeutic potential.
单纯疱疹病毒1型（HSV-1）是一种具有强大复制能力、基因组载荷大（≥30 kb）且毒性低的DNA病毒，使其成为癌症基因治疗中的一种重要载体。临床批准的溶瘤HSV-1（oHSV-1）变体，如T-VEC和G47Δ，在局部肿瘤中显示出安全性和有效性，但在治疗转移性疾病方面面临挑战。为了解决这个问题，下一代oHSV-1设计专注于通过递送多个外源基因实现精准靶向和免疫重塑。在这篇综述中，我们概述了oHSV-1作为基因递送平台的固有特性，重点介绍其基因改造策略、临床应用中的安全挑战以及最大化其治疗潜力的未来方向。
