What is RNA interference (RNAi)?

RNAi is a biological process that occurs naturally within our cells to help regulate gene expression. The mechanism by which RNAi mediates its biological function is specific targeting of messenger RNA (mRNA) molecules, which carry the instructions cells need to make proteins out of the genetic manual encoded in our DNA.

Our short interfering RNA (siRNA) therapeutics are synthetic molecules that harness this cellular process to silence the expression of disease-associated genes in a highly specific manner. An siRNA medicine designed to target a specific gene will, as part of an RNA-induced silencing complex (RISC), bind to its target mRNA and trigger its degradation. As a result, no disease-associated protein will be produced in the cell.

RNA Interference

RNAi medicines are next-generation therapeutics, and their design is markedly accelerated relative to traditional drug modalities because it is based on the human genetic code, which we now know. Other advantages of RNAi therapeutics include:

  • high specificity against their target gene, thus minimising potential off-target effects
  • no druggability issues, being able to silence virtually any gene in the genome
  • long duration of action, supporting infrequent administration and reduced patient burden
  • reversible effects (no changes to DNA)
  • good safety profile

Cell-type specific delivery to the liver

An additional level of specificity can be achieved by coupling siRNA molecules to delivery systems for cell-type specific targeting. Our siRNA constructs are conjugated to GalNAc (N-Acetylgalactosamine) moieties, which mediate highly specific delivery to hepatocytes in the liver. As the liver is a highly active organ, hepatocyte targeting unlocks opportunities in a wide variety of therapeutic areas.

This cell-type specificity spares other cell types in the body and ensures that therapeutic levels of the therapeutic reach target cells. Our siRNA medicines also incorporate optimised chemistries to maximise their therapeutic activity and, together with GalNAc, enable sub-cutaneous administration.

Selecting the right target gene

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