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Generation of a Vero-Based Packaging Cell Line to Produce SV40 Gene Delivery Vectors for Use in Clinical Gene Therapy Studies

机译:基于Vero的包装细胞系的产生以生产用于临床基因治疗研究的SV40基因递送载体

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摘要

Replication-defective (RD) recombinant simian virus 40 (SV40)-based gene delivery vectors hold a great potential for clinical applications because of their presumed non-immunogenicity and capacity to induce immune tolerance to the transgene products in humans. However, the clinical use of SV40 vectors has been hampered by the lack of a packaging cell line that produces replication-competent (RC) free SV40 particles in the vector production process. To solve this problem, we have adapted the current SV40 vector genome used for the production of vector particles and generated a novel Vero-based packaging cell line named SuperVero that exclusively expresses the SV40 large T antigen. SuperVero cells produce similar numbers of SV40 vector particles compared to the currently used packaging cell lines, albeit in the absence of contaminating RC SV40 particles. Our unique SV40 vector platform named SVac paves the way to clinically test a whole new generation of SV40-based therapeutics for a broad range of important diseases.
机译:基于复制缺陷型(RD)重组猿猴病毒40(SV40)的基因传递载体由于其假定的非免疫原性和诱导人类对转基因产物的免疫耐受的能力而在临床上具有巨大的潜力。然而,由于缺乏在载体生产过程中产生无复制能力(RC)的SV40颗粒的包装细胞系而阻碍了SV40载体的临床使用。为了解决这个问题,我们调整了当前用于生产载体颗粒的SV40矢量基因组,并生成了一种新的基于Vero的包装细胞系,名为SuperVero,专门表达SV40大T抗原。尽管没有污染RC SV40颗粒,但与目前使用的包装细胞系相比,SuperVero细胞可产生相似数量的SV40矢量颗粒。我们独特的名为SVac的SV40载体平台为临床测试基于SV40的新一代药物治疗各种重要疾病铺平了道路。

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