Small Interfering RNA (siRNA)

Structure and properties

Small interfering RNA (siRNA) is a short, synthetically produced RNA fragments consisting of approximately 21 to 25 nucleotides. The siRNA has a complementary sequence to a target mRNA in the human body and is usually administered in double-stranded form.

Effects

The sequence-specific siRNA leads to selective degradation of the complementary mRNA in the organism. Thus, gene expression is inhibited and a specific protein is not produced, indirectly inducing a pharmacologic effect. This physiological mechanism is also known as RNA interference (RNAi) and is effective for up to one week. In principle, any gene in the body can be silenced using this approach, allowing a variety of therapeutic applications. One obstacle is the fact that naked siRNA cannot cross cell membranes due to its negative charge. In addition, the RNA is enzymatically degraded in the blood and can cause side effects. Therefore, chemical modification of the RNA and the use of modern drug-delivery systems that deliver the siRNA to its site of action and into cells (known as transfection) are crucial.

Active Agents

  • Patisiran (Onpattro)
  • Givosiran (Givlaari)