Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures orthotopically transplanted mouse HCC.

Cancer Gene Therapy
Y TianDe-Qi Xu

Abstract

The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy.

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Citations

Apr 7, 2016·International Journal of Microbiology·Sebastian FelgnerSiegfried Weiss
Apr 24, 2013·Analytical Biochemistry·Kumaran NarayananEdmund Ui Hang Sim
Oct 1, 2016·Chonnam Medical Journal·Jin Hai Zheng, Jung-Joon Min
Jul 9, 2020·Cancer Medicine·Jiwei SunLili Chen
Aug 9, 2020·International Journal of Nanomedicine·Lingling OuShaoqiang Lin
Mar 20, 2021·Frontiers in Oncology·Fereshteh BadieHamed Mirzaei
May 15, 2021·Seminars in Cancer Biology·Vipin Chandra KaliaJung-Kul Lee

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