Alnylam has outlined their strategy for delivering siRNA to the central nervous system and other organs outside of the liver. The RNA specialist detailed how the coupling of its drug candidates permitted therapeutic suppression of target genes across the body in preclinical experiments in a recently paper published.
The delivery of siRNA to the liver is already possible with lipid nanoparticles and GalNAc conjugates, paving the way for the creation of authorised liver-targeted therapeutics. Alternative delivery techniques, on the other hand, are required if Alnylam and its competitors are to fulfil the full promise of siRNA and cure the wide range of disorders that could benefit from gene silencing.
Alnylam took a step forward in its extrahepatic delivery strategy earlier this year when it began a phase 1 trial of a prospective Alzheimer’s disease medication. The delivery system that underpins the Alzheimer’s candidate is the subject of a new research article.
Alnylam has attached 2-O-hexadecyl (C16) to siRNA molecules in order to get them to tissues other than the liver. The C16 method draws on a long history of lipophilic moieties being used to increase siRNA transport and uptake. Alnylam found an opportunity to improve the lipophilicity of chemically altered siRNA so that it could be delivered intracellularly.
Preclinical studies indicate that Alnylam is on to something. The biotech did a study on a mouse model of Alzheimer’s disease after demonstrating that the delivery method may cause knockdown in the CNS, eye, and lungs in animals. The suppression of the target gene lasted for 3 months and was linked to a decrease in an amyloid beta isoform. The findings were discussed by Kevin Fitzgerald, Ph.D., Alnylam’s chief scientific officer.
CNS diseases are among the most difficult to treat. These preclinical findings are encouraging because they imply siRNAs may have a function in treating illnesses of the CNS, eye, and lungs. Their CNS delivery platform has a long lifespan, which is especially beneficial in intrathecal administration settings where infrequent dosage is desired, Fitzgerald said in a release.
