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感染性重组单纯疱疹病毒 A 表达 p16 蛋白。

Infectious Recombinant Senecavirus A Expressing p16 Protein.

机构信息

Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China.

出版信息

Int J Mol Sci. 2023 Mar 24;24(7):6139. doi: 10.3390/ijms24076139.

Abstract

Senecavirus A (SVA) is an oncolytic RNA virus, and it is the ideal oncolytic virus that can be genetically engineered for editing. However, there has not been much exploration into creating SVA viruses that carry antitumor genes to increase their oncolytic potential. The construction of SVA viruses carrying antitumor genes that enhance oncolytic potential has not been fully explored. In this study, a recombinant SVA-CH-01-2015 virus (p15A-SVA-clone) expressing the human p16 protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was successfully rescued and characterized. The recombinant virus, called SVA-p16, exhibited similar viral replication kinetics to the parent virus, was genetically stable, and demonstrated enhanced antitumor effects in Ishikawa cells. Additionally, another recombinant SVA virus carrying a reporter gene (iLOV), SVA-iLOV, was constructed and identified using the same construction method as an auxiliary validation. Collectively, this study successfully created a new recombinant virus, SVA-p16, that showed increased antitumor effects and could serve as a model for further exploring the antitumor potential of SVA as an oncolytic virus.

摘要

塞内卡病毒 A(SVA)是一种溶瘤 RNA 病毒,是可进行遗传修饰的理想溶瘤病毒。然而,目前对于构建携带抗肿瘤基因的 SVA 病毒以提高其溶瘤能力的研究还较少。构建携带抗肿瘤基因以增强溶瘤能力的 SVA 病毒的研究还不充分。在这项研究中,成功拯救并鉴定了表达人 p16 蛋白(也称为细胞周期依赖性蛋白激酶抑制剂 2A(CDKN2A))的重组 SVA-CH-01-2015 病毒(p15A-SVA-clone)。这种重组病毒称为 SVA-p16,其复制动力学与亲本病毒相似,遗传稳定,并在 Ishikawa 细胞中显示出增强的抗肿瘤作用。此外,还使用与辅助验证相同的构建方法构建并鉴定了携带报告基因(iLOV)的另一种重组 SVA 病毒 SVA-iLOV。总之,这项研究成功地创建了一种新型重组病毒 SVA-p16,该病毒显示出增强的抗肿瘤作用,可作为进一步探索 SVA 作为溶瘤病毒的抗肿瘤潜力的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6941/10093924/e9fcbfb71e74/ijms-24-06139-g001.jpg

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