The targeted delivery of short interfering RNA (siRNA) has tremendous therapeutic potential with the development of effective delivery vectors a critical step towards clinical application.  In this study, various specially designed amphiphiles consisting of dendritic cationic peptides and a hydrophobic linker were synthesized and evaluated as potential siRNA vectors.  By systematically varying the length and identity of the hydrophobic region, vectors capable of efficient transfection were identified.  Dependent upon the size of the dendritic peptide domain, the vectors were shown by transmission electron microscopy (TEM) to assemble with siRNA into either fibrillar, liposomal, or micellar structures.  In comparison to other amphiphilic systems, our specially designed amphiphiles displayed minimal toxicity and efficient in vitro gene-silencing across multiples cell lines.  Co-formulation of the dendritic amphiphiles with amphiphiles bearing either poly-(ethylene glycol) (PEG) for increased serum stability or linear cell-penetrating peptides (CPPs) for enhanced cell uptake was investigated in order to evaluate the potential of these vectors for in vivo application.

Specially designed peptide amphiphiles for efficient siRNA delivery

248th National Meeting (2014)

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