2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

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TechConnect Summit
Clean Technology 2008

Delivery systems for enhanced siRNA delivery

A-L. Bolcato-Bellemin, M-E. Bonnet, J-P. Behr, P. Erbacher
Polyplus-transfection, FR

Keywords:
siRNA, polyethylenimine, in vivo, cationic lipids

Abstract:
To fully exploit the vast potential of RNA interference, the development of safe and efficient reagent to deliver small amount of siRNA is necessary. We have explored the potential of in vivo-jetPEI™, an optimized linear polyethylenimine for the delivery of siRNA in animal models. Our results show an efficient delivery of siRNA in different organs. We also demonstrate that the biodistribution in the target organs is dependent on the injection route. Moreover, we have designed sticky siRNA (ssiRNA) mimicking the structure of long double-stranded DNA in order to increase delivery of siRNA and silencing efficiency with in vivo-jetPEI™. Our modified siRNA have the ability to reversibly oligomerize using 3’ complementary overhangs and to mimic DNA structure. We show that ssiRNAs are more effective than siRNAs when using in vivo-jetPEI™ as a delivery reagent. We have also developed another reagent based on cationic lipids for efficient delivery of siRNA in vitro at picomolar concentration and we are working on an in vivo formulation of this promising agent. Taken together, our data demonstrate the great potential of polymers and cationic systems to deliver siRNAs into animal models, highlighting the potency of these molecules as non-viral reagents of choice for nucleic acid therapy.


Nanotech 2008 Conference Program Abstract