A Salmonella Typhimurium mutant strain capable of RNAi delivery: higher tumor-targeting and lower toxicity.
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.
The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China.
Xiawei
X
Cheng
The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China.
Xiaoxin
X
Zhang
The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China.
Yuqiang
Y
Zhou
The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China.
Chunmei
C
Zhang
The State Key Laboratory of Pharmaceutical Biotechnology; School of Life Science and School of Stomatology; Affiliated Stomatological Hospital; Nanjing University; Nanjing, Jiangsu, PR China; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc.; Changzhou, Jiangsu, PR China.
Zi-Chun
ZC
Hua
D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics*; D013154:Spleen / Q000473:pathology
D001428:Bacterial Vaccines; D034741:RNA, Small Interfering; C465023:VNP 20009; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
PhoP/PhoQ gene; RNA interference; SalmonellaTyphimurium; anti-tumor; delivering system; safety; tumor-targeting