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Summary

Gene silencing refers to the phenomenon that biological cells can inhibit the expression of a gene using various gene expression regulation mechanisms. There are two main types of gene silencing.

• Gene silencing at the transcriptional level

Gene silencing at the transcriptional level mainly includes DNA methylation, location effects, genomic imprinting, gene transfer, repeat-induced point mutations, and paramutation.

• Post-transcriptional gene silencing

Post-transcriptional gene silencing mainly includes co-inhibition and RNA silencing (including RNA interference, gene quelling, and unpaired DNA-mediated meiosis silencing, guided by small RNAs such as microRNA (miRNA), small interfering RNAs (siRNAs), Piwi-associated RNAs (piRNAs), and mRNA degradation, etc. For example, the 3' untranslated region (3'UTR) of many mRNAs can bind to miRNA to reduce mRNA translation and achieve gene silencing.

In biological research, to study the function of a gene, researchers will use RNA interference or CRISPR gene-knocking technology to achieve gene silencing, greatly reduce the performance of the target gene to detect its influence, and then infer the function of the target gene. Compared with the expression of target genes completely removed by gene deletion, although the expression of target genes was inhibited by gene knocking, it still retained a certain degree of expression.

In conclusion, gene silencing is an important way of gene expression regulation and a self-protection mechanism for organisms at the level of gene regulation. It is common in foreign DNA invasion, virus infection, DNA transposition, and rearrangement. An in-depth study of gene silencing can help researchers to further reveal the nature of gene expression regulation of organisms, and overcome the phenomenon of gene silencing so that exogenous genes can be more effectively expressed according to people's needs. Gene silencing can effectively inhibit the expression of harmful genes in gene therapy to achieve the purpose of disease treatment, so the study of gene silencing has extremely important theoretical and practical significance.

Application

• The study of gene therapy for lung cancer is a hot issue in the medical field. Ras protein is a kind of GTP-binding protein encoded by the Ras gene, which has GTPase activity and is an important signal transduction molecule. The occurrence of human lung cancer is closely related to the expression of the KRaV12 mutant gene. Some researchers infected lung cancer cell line H441 with siRNA targeting K-RasV12, resulting in decreased K-Ras mRNA expression and Ras protein expression levels. Compared with the control group, the cell proliferation rate of transfected cells was decreased, and the number of apoptosis was increased. In vivo experiments, tumor growth in nude mice can also be inhibited by siRNA.
• The drug named Givosiran is a double-stranded siRNA targeting δ-amino ketovalerate synthase 1 (ALAS1, an important enzyme in the production of blood matrix), which can specifically degrade ALAS1 mRNA, produce gene silence phenomenon, reduce the accumulation of amino ketovalerate acid (ALA) and porphyria, and improve the symptoms of acute porphyria attack. In 2019, the U.S. Food and Drug Administration approved an adult drug for the treatment of acute hepatic porphyria (AHP) and considers it a first in the field.

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