Alkane-modified short polyethyleneimine for siRNA delivery
Author(s)Anderson, Daniel; Schroeder, Avraham Dror; Dahlman, James; Sahay, Gaurav; Love, Kevin T; Jiang, Shan; Eltoukhy, Ahmed Atef; Levins, Christopher G.; Wang, Yingxia; ... Show more Show less
MetadataShow full item record
RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer–lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering
Journal of Controlled Release
Schroeder, Avi et al. “Alkane-Modified Short Polyethyleneimine for siRNA Delivery.” Journal of Controlled Release 160.2 (2012): 172–176.
Author's final manuscript