Versatile cationic lipids for siRNA delivery through Biotage Isolera耐士科技

Here we report the development of a class of structurally versatile cationic lipopolyamines designed specifically for delivery of siRNA which show high levels of target transcript knockdown in a range of cell types in vitro. A primary benefit of these lipids is the ease with which they may be covalently modified by the addition of functional molecules. For in vivo applications one of the core lipids (Staramine) was modified with methoxypolyethylene glycols (mPEGs) of varying lengths. Upon systemic administration, PEGylated Staramine nanoparticles containing siRNA targeting the caveolin-1 (Cav-1) transcript caused a reduction of the Cav-1 transcript of up to 60%, depending on the mPEG length, specifically in lung tissue after 48 h compared to treatment with non-silencing siRNA. In addition, modification with mPEG reduced toxicity associated with intravenous administration. The ability to produce a high level of target gene knockdown in the lung with minimal toxicity demonstrates the potential of these lipopolyamines for use in developing RNAi therapeutics for pulmonary disease.