A Salmonella Typhimurium mutant strain capable of RNAi delivery: Higher tumor-targeting and lower toxicity |
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| Authors: | Xiawei Cheng Xiaoxin Zhang Yuqiang Zhou Chunmei Zhang Zi-Chun Hua |
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| Institution: | 1.The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China;2.Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc.; Changzhou, Jiangsu, PR China |
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| Abstract: | Bacteria are highly versatile and useful tools that could deliver short interfering RNA. In this study, a phoP/phoQ double-deleted Salmonella Typhimurium named VNP(PhoP/Q−) based on the genetic background of VNP20009. The biological safety and function of VNP(PhoP/Q−) were also analyzed. Our study revealed the following results: (1) VNP(PhoP/Q−) exhibited lower titers in tumor-free livers and spleens than VNP20009, (2) The survival of VNP(PhoP/Q−) in macrophages and 4T1 tumor cells was significantly reduced compared with that of VNP20009, (3) The tumor-targeting ability of VNP(PhoP/Q−) was significantly enhanced compared with that of VNP20009, and the anticancer effects of VNP(pPhoP/Q−) and VNP20009 on tumor-bearing mice were similar, (4) VNP(PhoP/Q−) could release an shRNA-expressing plasmid and express the EGFP reporter gene in tumor tissue. Therefore, VNP(PhoP/Q−) exhibited a better safety level in tumor-free mice and elicited an anti-tumor effect on tumor-bearing mice. Moreover, VNP(PhoP/Q−) could release an shRNA-expressing plasmid into the cytoplasm of host cells to silence targeted genes. |
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| Keywords: | Salmonella Typhimurium RNA interference delivering system PhoP/PhoQ gene anti-tumor tumor-targeting safety |
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