Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery

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Author
Lee, Hyukjin
Lytton-Jean, Abigail K. R.
Chen, Yi
Love, Kevin T.
Park, Angela I.
Karagiannis, Emmanouil D.
Sehgal, Alfica
Querbes, William
Zurenko, Christopher S.
Jayaraman, Muthusamy
Peng, Chang G.
Charisse, Klaus
Borodovsky, Anna
Manoharan, Muthiah
Donahoe, Jessica S.
Truelove, Jessica
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nnano.2012.73Metadata
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Lee, H., A. K. R. Lytton-Jean, Y. Chen, K. T. Love, A. I. Park, E. D. Karagiannis, A. Sehgal, et al. 2013. “Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery.” Nature nanotechnology 7 (6): 389-393. doi:10.1038/nnano.2012.73. http://dx.doi.org/10.1038/nnano.2012.73.Abstract
Nanoparticles are employed for delivering therapeutics into cells1,2. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell specific internalization, excretion, toxicity, and efficacy3-7. A variety of materials have been explored for delivering small interfering RNAs (siRNAs) - a therapeutic agent that suppresses the expression of targeted genes8,9. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, lack of tissue specificity and potential toxicity10-12. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer targeting ligands (such as peptides and folate) on the nanoparticle surface can be precisely controlled. We show that at least three folate molecules per nanoparticle is required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t1/2 ∼ 24.2 min) than the parent siRNA (t1/2 ∼ 6 min).Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898745/pdf/Terms of Use
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