Micro-ribonucleic acids microRNAs (microRNA) are a type of single-stranded small ribonucleic acid molecules with a length of about 19-23 nucleotides; they are located at the non-coding region of a genome and evolutionarily highly conserved, and can regulate the gene expression by inhibiting the translation process of target genes and are closely related to many normal physiological activities of animals, such as the individual development, tissue differentiation, cell apoptosis, and energy metabolism of organisms, and meanwhile are closely associated with the occurrence and development of many diseases. Since lin-4 and let-7, which are involved in the regulation of the timing development of nematodes, have been found, microRNA has gradually become the research hotspot with respect to the regulation of mRNA stability and protein translation, which was chosen as one of the ten annual scientific breakthroughs by journal Science two times in 2002 and 2003, respectively. It is now predicted that microRNA can regulate at least 5300 human genes, that is, 30% of all of the genes. As the research moves along, more and more microRNAs are found, in which the relationship between microRNAs and tumor becomes gradually the focus of research, and it has been found that several microRNAs are highly related to chronic lymphocytic leukemia, lung cancer, breast cancer, and colon cancer by negatively regulating the expression of genes.
Small interfering ribonucleic acids (small interfering RNA, siRNA) are a type of double-stranded RNA molecules composed of more than 20 nucleotides, which can exert the effect of silencing gene expression by specifically degrading the messenger ribonucleic acids (messenger RNA, mRNA) of target genes. This process is called RNA interference, RNAi.
RNA interference is a mode of post-transcriptional regulation of genes. SiRNA can specifically recognize target genes thereof and can recruit a protein complex which is called silencing complex (RNA induced silencing complex, RISC). RISC comprises ribonuclease and the like, which can specifically and efficiently inhibit the expression of genes through the manner of targeted cleaving homologous mRNA. Since the use of RNA interference technology can specifically knock out or shut down the expression of particular genes, this technology has been widely used in the fields of biomedical experimental research and therapy of various diseases.
MicroRNA and siRNA Involved in the Therapy of Diseases
Current studies have proved that the progress of diseases can be interrupted or delayed through regulating the content of particular microRNAs in the body of an organism or through injecting exogenous siRNA. They both can participate in the treatment and prevention of diseases through affecting the expression of particular proteins. For instance, the expression of miR-206 in skeletal muscles can relieve the injury or loss of motor neurons, the effect of which is mainly realized by promoting and activating the generation of links of neurons between muscles, thus treating amyotrophic lateral sclerosis (also called ALS); and down-regulation of the expression of miR-122 in liver can exert therapeutic effects on hepatitis C; and since the overexpression of Bcl-2 resulted by the loss of miR-15 and miR-16 is an important mechanism for the occurrence of human chronic lymphatic leukemia (CLL), the overexpression of miR-15 and miR-16 in organisms can exert therapeutic effects on CLL.
Although there are many achievements on the study and development of microRNA and siRNA, many problems still exist before their practical application as pharmaceuticals in medical treatment, especially how to improve the efficiency of delivering such pharmaceuticals; and in general their efficacy can be exerted only when administration at a focus site is required, but this therapeutic method of in situ administration severely limits the application of the pharmaceuticals.