4.4 Article

Phage-Derived Oncolytic Viruses with 3C from Seneca Valley Virus for Targeted Therapy of Cervical Cancer

Journal

ADVANCED THERAPEUTICS
Volume 5, Issue 8, Pages -

Publisher

WILEY
DOI: 10.1002/adtp.202200059

Keywords

cervical cancer; gene therapy; M13 phage; Phage-derived oncolytic viruses; Seneca Valley Virus 3C protein

Funding

  1. Natural Science Foundation of Jiangsu Province [BK20200950]
  2. Innovative and Entrepreneurial Team Project of Jiangsu Province
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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In this study, a new M13 phage-based oncolytic virus was constructed and shown to target and kill tumor cells in both in vitro and in vivo experiments. The engineered M13 phage may be further modified to inhibit the growth of tumor cells, providing a promising option for targeted oncolytic therapy.
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.

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