Press release
Alnylam Announces Publication of Preclinical Results Based on Novel Conjugate Technology That Facilitates Delivery of Short Interfering RNA to the Central Nervous System and Other Extrahepatic Tissues
- Conjugation of 2’-O-hexadecyl (C16) to siRNA Enables Therapeutic Silencing of Target Genes Outside the Liver with Infrequent Dosing in Rodents and
About this update from Alnylam Pharmaceuticals, Inc.
[{"type":"text","content":"\n- Conjugation of 2’-O-hexadecyl (C16) to siRNA Enables Therapeutic Silencing of Target Genes Outside the Liver with Infrequent Dosing in Rodents and Non-Human Primates -\n\n- In a Mouse Model of Alzheimer’s Disease, C16-siRNA Targeting the Amyloid Beta Precursor Protein Gene Led to Potent and Durable Knockdown in the CNS and Ameliorated Physiological and Behavioral Deficits -\n\n- Sustained Knockdown Observed May Allow for Infrequent Dosing of C16-siRNAs in Humans and Warrants Continued Investigation in Clinical Trials, Including an Ongoing Phase 1 Study of ALN-APP in Alzheimer’s Disease, in Which Dosing Has Been Initiated -\n\n CAMBRIDGE, Mass.--(BUSINESS WIRE)--\nAlnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that data from its preclinical research on delivery of lipophilic short interfering RNA (siRNA) conjugates to extra-hepatic tissues, including the central nervous system (CNS), were published online in Nature Biotechnology. The published data provide early evidence of a potential role for 2'-O-hexadecyl (C16)-conjugated siRNAs in treating diseases of the CNS, eye, and lung. The framework for designing siRNAs for extrahepatic applications leverages Alnylam’s decades long investment in the siRNA delivery platform. The full manuscript titled “Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates” will appear in the June issue of Nature Biotechnology.\n\nThe published data show that conjugation of C16 to metabolically stable siRNAs enables robust and long-lasting gene silencing in the CNS, eye and lung in rodents and non-human primates (NHPs) with broad cell type specificity and a favorable nonclinical safety profile. The manuscript also provides evidence demonstrating C16-siRNA-mediated gene silencing translates into efficacy in an in vivo mouse model of neurodegenerative disease.\n\n“Diseases of the CNS are some of the most difficult to treat. Thus, we are encouraged by these preclinical findings as they suggest siRNAs may have a role in treating diseases impacting the CNS, the eye, and the lung,” said Kevin Fitzgerald, Ph.D., EVP, Chief Scientific Officer. “Our CNS delivery platform provides long durability, which is particularly advantageous in settings of intrathecal administration, where infrequent dosing is desirable. Leveraging this platf...