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

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TechConnect Summit
Clean Technology 2008

Toward in vivo Targeting Delivery of siRNA for Efficient Cancer Therapy

O. Taratula, P. Kirkpatrick, R. Salva, I. Pandya, T. Minko, H. He
Rutgers-Newark University, US

Keywords:
siRNA, delivery, extracellular, steric, lateral stability

Abstract:
There is an increasing enthusiasm for developing therapies based on RNA interference (RNAi). However, the main obstacle in siRNA therapy is RNA delivering to the cytoplasm where it can guide sequence-specific mRNA degradation. An efficient, nontoxic delivery strategy has not been developed yet. Attempts to develop effective nonviral vectors for in vivo delivery of nucleic acids through a systemic route are hampered by difficulties of combining of high extracellular stability with ready availability of the nucleic acids following entry into cells. Here we report a targeted siRNA delivery vector that display good extracellular stability and intracellular bioavailability for efficient gene silencing. SiRNAs were packaged into discrete nanoparticles by polypropyleneimine dendrimers. Modification of the siRNA nanoparticles with dithiol containing crosslinker and further PEGylation of crosslinked condensates provided their sterical and lateral stabilization. In order to specifically delivery the siRNA nanoparticles to cancer cells, the distal end of PEG was modified with a targeting agent, such as LHRH. The enhancement of the internalization of LHRH modified condensates was demonstrated. The ability of the delivered siRNA to silence their targeted mRNA was shown by PCR experiment. We envision this approach can be used in vivo systematic delivery of siRNAs for efficient cancer therapy.


Nanotech 2008 Conference Program Abstract