Gene Silencing

Gene silencing is a process in which a gene is switched off. It is different from gene mutation. In fact, in gene silencing the mechanisms regulating gene expression are changed so that the gene will not be expressed and, in other words, the gene expression is down-regulated or the gene is turned off. It is believed that innate gene silencing has been a tool for protecting the genomes of organisms from infectious DNA elements such as viruses during the evolution. In other words, gene silencing has been an innate cellular immune surveillance system. Gene silencing has been proposed as a method for gene therapy in different diseases.

Because genes are regulated by transcriptional and posttranscriptional mechanisms, gene silencing can be a transcriptional or posttranscriptional procedure. Gene silencing at the transcriptional level is made by creating an environment with modified histone proteins. In this environment, gene cannot be expressed because of changes in transcriptional agents. For gene silencing at the posttranscriptional level, the messenger ribonucleic acid (mRNA), which is the transcriptional result of that gene, must be destroyed to stop translational process.

There are different methods for gene silencing at the transcriptional and posttranscriptional levels. Using oligodeoxynucleotides is a way for performing gene silencing as a therapeutic tool. Synthetic oligodeoxynucleotides are used for gene-specific expression interruption. Introduction of gene-specific oligodeoxynucleotides with their binding to target gene or mRNA inhibits transcription or translation of that specific gene. This strategy is called antisense strategy. Another strategy, which is called antigenene strategy, is based on avoidance of interaction between transcription factor and a target gene which will result in inactivation of that gene.

The most famous gene silencing method is RNA interference (RNAi) which has brought hopes for gene therapy of many diseases. The discovery of RNAi has been one of the transforming events in biomedical sciences. This novel technology can result in gene silencing or even omitting functions of specific sequences from the genome. RNAi technology involves introduction of double-stranded RNA result in inhibition of gene expression at the posttranscriptional level. In order to target mRNA for destruction and perform a posttranscriptional gene silencing, short interference RNA (siRNA) or silencing RNA is used. siRNA is a short oligonucleotide of about 19 to 23 nucleotides with a high specificity for target genes which are supposed to be turned off. There are many ongoing trials to test the capability of RNAi for curing several diseases such as cancers and AIDS.

Although gene silencing is an ancient immune cellular system, man-made gene silencing technology is a state-of-the-art approach for meddling with specific gene expression with applications in treatment of many important diseases.