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Gene silencing


Gene silencing is a general term used to describe the regulation of gene expression. In particular, this term refers to the ability of a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and diseases, such as infectious diseases and neurodegenerative disorders.

Gene silencing is often considered the same as gene knockout. When genes are silenced, their expression is reduced. In contrast, when genes are knocked out, they are completely erased from the organism's genome and, thus, have no expression. Gene silencing is considered a gene knockdown mechanism since the methods used to silence genes, such as RNAi, CRISPR, or siRNA, generally reduce the expression of a gene by at least 70% but do not completely eliminate it. Methods using gene silencing are often considered better than gene knockouts since they allow researchers to study essential genes that are required for the animal models to survive and cannot be removed. In addition, they provide a more complete view on the development of diseases since diseases are generally associated with genes that have a reduced expression.

Antisense oligonucleotides were discovered in 1978 by Paul Zamecnik and Mary Stephenson.Oligonucleotides, which are short nucleic acid fragments, bind to complementary target mRNA molecules when added to the cell. These molecules can be composed of single-stranded DNA or RNA and are generally 13–25 nucleotides long. The antisense oligonucleotides can affect gene expression in two ways: by using an RNase H-dependent mechanism or by using a steric blocking mechanism. RNase H-dependent oligonucleotides cause the target mRNA molecules to be degraded, while steric-blocker oligonucleotides prevent translation of the mRNA molecule. The majority of antisense drugs function through the RNase H-dependent mechanism, in which RNase H hydrolyzes the RNA strand of the DNA/RNA heteroduplex. This mechanism is thought to be more efficient, resulting in an approximately 80% to 95% decrease in the protein and mRNA expression.


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