The aim of the present study was to identify the effectiveness of lentivirus‑mediated RNA interference (RNAi) targeting mouse tumor necrosis factor‑α (TNF‑α). RNAi lentivirus was used in vitro to transfect RAW264.7 cells, and the expression of TNF‑α, interleukin (IL)‑1β and IL‑6 mRNAs and TNF‑α protein in RAW264.7 cells was measured by reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and enzyme‑linked immunosorbent assay, respectively. In vivo, mice with collagen‑induced arthritis (CIA) were injected intravenously with RNAi lentivirus, and CIA arthritis scores and the serum levels of TNF‑α were detected. Additionally, joint tissues were subjected to pathological examination. In the cells, the expression level of TNF‑α mRNA in the RNAi lentivirus group was 0.29±0.02, which was significantly lower than that of the lentivirus negative control (0.93±0.01; t=25.4, P<0.001). In the mice, the serum TNF‑α level in the RNAi lentivirus group was 249.25±11.22 ng/ml, which was significantly lower than that of the negative control group (381.86±6.28 ng/ml; P<0.05). However, no difference in IL‑1α and IL‑6 mRNA levels was identified among the groups (t=1.00, P=0.37; t=1.22, P=0.29). The CIA arthritis score in the RNAi lentivirus group was significantly reduced compared with those in the control and negative control groups (P<0.05). Furthermore, the arthritis scores in the RNAi lentivirus and positive control groups continued to decrease for ≥2 weeks, and the serum TNF‑α levels in the RNAi lentivirus and positive control groups were 31.58±2.18 and 35.21±2.25 pg/ml, which were significantly lower than those in the negative control group (46.62±3.02 pg/ml; P<0.05). Thus, targeting of the TNF‑α gene in mice via lentivirus-mediated RNAi in vitro and in vivo achieved TNF‑α gene downregulation, which indicates that lentivirus‑mediated RNA interference may be an effective form of gene therapy against rheumatoid arthritis.

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