Drug name: siRNA


Related CSCTT Targets

Oct4 [ref.1]Q01860
SMO [ref.2]Q99835
EZH2 [ref.3]Q15910
PKCδ [ref.4]Q05655
DCLK1 [ref.5]O15075
Notch1 [ref.6,7,8]P46531
Notch4 [ref.7]Q99466
Notch3 [ref.9]Q9UM47
Mcl-1 [ref.10]Q07820
β-Catenin [ref.11]P35222
Snail [ref.12]O95863
LGR5 [ref.13]O75473
ARTN [ref.14]Q5T4W7
TB-4 [ref.15]P62328
ZEB1 [ref.16]P37275
ZEB2 [ref.16]O60315
PKCε [ref.17]Q02156
Nanog [ref.17]Q9H9S0
microRNA 21 [ref.18]
FOXM1 [ref.19]Q08050

Introduction

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length. siRNA plays many roles, but it is most notable in the RNA interference (RNAi) pathway, where it interferes with the expression of specific genes with complementary nucleotide sequences. siRNA functions by causing mRNA to be broken down after transcription, resulting in no translation. siRNA also acts in RNAi-related pathways, e.g., as an antiviral mechanism or in shaping the chromatin structure of a genome. The complexity of these pathways is only now being elucidated.

siRNAs have a well-defined structure: a short (usually 20 to 24-bp) double-stranded RNA (dsRNA) with phosphorylated 5' ends and hydroxylated 3' ends with two overhanging nucleotides. The Dicer enzyme catalyzes production of siRNAs from long dsRNAs and small hairpin RNAs. siRNAs can also be introduced into cells by transfection. Since in principle any gene can be knocked down by a synthetic siRNA with a complementary sequence, siRNAs are an important tool for validating gene function and drug targeting in the post-genomic era.

Given the ability to knock down, in essence, any gene of interest, RNAi via siRNAs has generated a great deal of interest in both basic and applied biology. There are an increasing number of large-scale RNAi screens that are designed to identify the important genes in various biological pathways. Because disease processes also depend on the activity of multiple genes, it is expected that in some situations turning off the activity of a gene with an siRNA could produce a therapeutic benefit.

Phase I results of the first two therapeutic RNAi trials (indicated for age-related macular degeneration, aka AMD) reported at the end of 2005 that siRNAs are well tolerated and have suitable pharmacokinetic properties.

Small interfering RNASchema

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Reference

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