Skip to main content
Premium Trial:

Request an Annual Quote

Alnylam Presents Animal Data on siRNA Delivery via Inhalation, Adds PH1 to Pipeline


NEW YORK (GenomeWeb) – Alnylam Pharmaceuticals this week released new preclinical data showing that a next-generation version of its GalNAc conjugates has the potential to deliver siRNAs against liver targets when administered via inhalation.

The company also announced that it has added primary hyperoxaluria type 1 (PH1), a rare kidney disease, to its pipeline and released rodent data demonstrating an RNAi approach to treating the disease.

The GalNAc approach is based on a sugar modification called N-acetyl galactosamine, which is a high-affinity ligand for the asialoglycoprotein receptors that are expressed on the surface of hepatocytes in all mammals. Alnylam has been using conjugates to enable subcutaneous delivery of its new drug candidates, while also developing a newer version with enhanced stability.

According to the company, siRNAs formulated with the improved GalNAc conjugates and targeting either Factor VII or transthyretin — the gene that is mutated in TTR-mediated amyloidosis — were able to knock down their liver-based targets in mice when administered via inhalation.

Notably, the level and duration of knockdown achieved was comparable to that seen when the molecules were delivered subcutaneously.

"These data provide proof of concept for inhalation as a needle-less, non-invasive approach for administration of RNAi therapeutics targeting liver disease genes," Alnylam said.

PH1 is rare, inherited autosomal-recessive condition characterized by the liver's inability to metabolize a precursor of oxalate due to disruption of an enzyme called alanine-glyoxylate aminotransferase 1 (AGT1). As a result, calcium oxalate builds up in renal tubules causing kidney stones and fibrosis.

According to Alnylam, its PH1 program will focus on silencing glycolate oxidase, and in rodent studies it was able to achieve robust knockdown of the target with substantial reductions in urinary oxalate levels.

The company aims to select a drug candidate for the program by mid-2015, with an investigational new drug application filed in 2016.

The Scan

Machine Learning Helps ID Molecular Mechanisms of Pancreatic Islet Beta Cell Subtypes in Type 2 Diabetes

The approach helps overcome limitations of previous studies that had investigated the molecular mechanisms of pancreatic islet beta cells, the authors write in their Nature Genetics paper.

Culture-Based Methods, Shotgun Sequencing Reveal Transmission of Bifidobacterium Strains From Mothers to Infants

In a Nature Communications study, culture-based approaches along with shotgun sequencing give a better picture of the microbial strains transmitted from mothers to infants.

Microbial Communities Can Help Trees Adapt to Changing Climates

Tree seedlings that were inoculated with microbes from dry, warm, or cold sites could better survive drought, heat, and cold stress, according to a study in Science.

A Combination of Genetics and Environment Causes Cleft Lip

In a study published in Nature Communications, researchers investigate what combination of genetic and environmental factors come into play to cause cleft lip/palate.