Cancer gene therapy based on various gene delivery vectors has some potential but also has obvious disadvantages. In this study, a new M13 phage-based oncolytic virus is constructed that carried the RGD peptides to target tumor cells and the 3C gene of Seneca Valley virus (SVV) preceded by a eukaryotic initial transcriptional region (ITR) to transcribe an oncolytic protein to kill tumor cells. Recombinant virus particles of 1200 nm in length are obtained in large quantities by transfecting the recombinant M13 phage plasmid into the host BL2738 and are investigated in vitro in tumor cells and in vivo in tumor-bearing mice to evaluate their antitumor effect. The experiments using Hela cells confirm that the engineered M13 phage can target and enter Hela cells, and express the SVV 3C protein, resulting in apoptosis of target cells by upregulating the expression of caspase 3. Furthermore, the results of experiments in vivo also show that the recombinant phage significantly inhibits the enhanced tumor volume in nude mice compared to the control groups. The M13 phage may be engineered to fuse with a variety of oncolytic proteins to inhibit the growth of tumor cells in the future, providing a promising phage-based targeted oncolytic reagent.

中文翻译：

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来自 Seneca Valley 病毒的 3C 噬菌体衍生溶瘤病毒用于宫颈癌的靶向治疗

基于各种基因传递载体的癌症基因治疗具有一定的潜力，但也存在明显的缺点。在这项研究中，构建了一种新的基于 M13 噬菌体的溶瘤病毒，该病毒携带 RGD 肽靶向肿瘤细胞和塞内卡谷病毒 (SVV) 的 3C 基因，在真核起始转录区 (ITR) 之前将溶瘤蛋白转录为杀死肿瘤细胞。通过将重组M13噬菌体质粒转染到宿主BL2738中大量获得长度为1200 nm的重组病毒颗粒，并在肿瘤细胞和荷瘤小鼠体内进行体外研究以评估其抗肿瘤作用。使用 Hela 细胞的实验证实，工程改造的 M13 噬菌体可以靶向并进入 Hela 细胞，并表达 SVV 3C 蛋白，通过上调 caspase 3 的表达导致靶细胞凋亡。此外，体内实验结果还表明，与对照组相比，重组噬菌体显着抑制了裸鼠肿瘤体积的增加。M13噬菌体可能被设计成与多种溶瘤蛋白融合，未来可抑制肿瘤细胞的生长，提供一种很有前景的基于噬菌体的靶向溶瘤试剂。