DsiRNA: Dicerna’s Therapy Platform
Discovering and delivering innovative RNAi therapies.
Dicerna has assembled a stable of innovative technologies with the goal of realizing the full clinical and commercial potential of RNAi therapies. Our innovative GalXCTM RNAi technology platform fuels a pipeline of promising, precisely targeted therapies designed to overcome many of the challenges of earlier generations of RNAi therapeutics.
Due to the asymmetry of the Dicer Substrate short-interfering RNAs (DsiRNAs) molecules, an enzyme known as Dicer binds them preferentially in only one orientation, resulting in the preferential incorporation of the Guide Strand into the RNAi machinery (known as RISC, or RNA-Induced Silencing Complex).
In this naturally occurring biological process, double-stranded RNA molecules induce the enzymatic destruction of the messenger RNA (mRNA) of a target gene that contains sequences that are complementary to one strand of the therapeutic double-stranded RNA molecule. The Company’s approach is to design proprietary double-stranded RNA molecules that have the potential to engage the enzyme Dicer, the initiation point for RNAi in the human cell cytoplasm, and initiate an RNAi process to silence a specific target gene. These proprietary molecules are generally referred to as DsiRNAs. Our GalXC RNAi platform utilizes a particular Dicer Substrate structure configured for subcutaneous delivery to the liver. Due to the enzymatic nature of RNAi, a single GalXC molecule incorporated into the RNAi machinery can destroy hundreds or thousands of mRNAs from the targeted gene.
Before incorporation into RISC, Dicer cleaves the blunt end of the DsiRNA, and the cleaved-off end of the molecule is discarded and degraded. With DsiRNAs, this small cleaved region lacks any function. The extended region at one end of the GalXC molecule is generally on the part of the molecule cleaved off by Dicer, and this region is engineered to provide additional pharmaceutical functionality to the GalXC molecules. For example, we can engineer enhanced immunosilencing activity, and can manufacture this region to bind serum albumin, improving the circulating half-life of a GalXC molecule.