Long‐lasting siRNA‐based down‐regulation of gene of interest can be achieved by lentiviral‐based expression vectors driving the production of short hairpin RNA (shRNA). We investigated an attractive therapeutic approach to target the expression of proinflammatory GMF by using lentiviral vector encoding GMF‐specific shRNA to reduce GMF levels in the spinal cord and brain of mice. To determine the effect of GMF‐shRNA on GMF protein levels, we performed quantitative ELISA analysis in brain and in thoracic, cervical and lumbar regions of spinal cord from mice followed by GMF‐shRNA (G‐shRNA) or control shRNA C‐shRNA) treatments. Our results show a marked reduction of GMF protein levels in brain and spinal cord of mice treated with GMF‐shRNA compared to control shRNA treatment. Thus, the down‐regulation of GMF by GMF‐shRNA was efficient and wide spread in CNS as evident by the significantly reduced levels of GMF protein in the brain and spinal cord of mice