siRNArelated

SiRNA-related topics cover the biology and applications of small interfering RNA (siRNA), a class of short, double-stranded RNA molecules that mediate RNA interference and gene silencing. In most organisms, siRNAs are about 21 to 23 nucleotides long and typically feature a 2-nucleotide 3' overhang. They guide sequence-specific degradation of complementary mRNA, reducing expression of the targeted gene.

Biogenesis and mechanism: In cells, long double-stranded RNA is processed by the enzyme Dicer into siRNA duplexes. One strand becomes the guide strand and is loaded into the RNA-induced silencing complex (RISC), while the passenger strand is discarded. Within RISC, an Argonaute protein (AGO2 in humans) uses the guide to recognize target mRNA and cleave it between nucleotides 10 and 11 of the guide. The seed region (nucleotides 2–8) plays a key role in target recognition and can influence off-target effects.

Sources and contexts: siRNA can originate from exogenous sources or be generated internally from synthetic duplexes or short hairpin RNA (shRNA) precursors. In mammals, long dsRNA can trigger antiviral responses, so therapeutic and experimental uses rely on carefully designed sequences and chemical modifications to minimize immune activation and improve stability.

Applications and challenges: SiRNA serves as a powerful tool for gene knockdown in research and has led to approved therapies delivered by lipid nanoparticles, such as patisiran. Challenges include delivering the molecules to specific tissues, achieving intracellular stability, avoiding off-target silencing, and limiting immune responses. Solutions involve optimized designs, chemical modifications (for example, 2'-O-methyl or 2'-fluoro), and advanced delivery systems.

Related terms: RNA interference, microRNA, shRNA, Dicer, Argonaute.