Alnylam Pharmaceuticals and researchers from the Massachusetts Institute of Technology (MIT) report findings that further development of lipidoid formulations for the systemic delivery of siRNAs.
This study identified key parameters affecting the pharmacodynamics of this type of formulation, including increasing the anchor length of synthesized PEG lipids, maximizing siRNA loading, and reducing particle size to more efficiently access hepatocytes, according to the scientists.
They also demonstrated that lipidoid formulations achieve delivery of greater than 90% of the administered siRNA dose to the liver and maintain robust in vivo activity following repeat administration over a period of several months, indicating no evidence of neutralizing antigenicity or tachyphylaxis.
Additionally, the investigators say that they were able to characterize the long-term stability of the formulation.
Lipidoids are a class of lipid-based molecules that are used to form nanoparticle formulations for systemic delivery of RNAi therapeutics. A previous study by Alnylam and MIT scientists showed successful delivery of siRNAs encapsulated in lipidoid formulations when administered in multiple animal species including mice, rats, and nonhuman primates.
Lipidoid formulations represent one of several approaches Alnylam is pursuing for systemic delivery of RNAi therapeutics. Additional approaches include other lipid nanoparticle formulations and siRNA conjugation strategies.
The company reports its most recent findings in Molecular Therapy.