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Polymeric Nanocarriers for siRNA Delivery: Challenges and Future Prospects

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Abstract:

Since the discovery of RNA interference in higher eukaryotes a decade ago, small interfering RNAs have been suggested to possess a large therapeutic potential. Small interfering RNAs can knock down expression of specific target genes by initiating mRNA degradation upon Watson-Crick base pairing with the target transcript in the cell cytoplasm. This sequence-specific regulation is promising for treatment of serious pathological conditions such as cancer, infections and inflammatory diseases. However, poor cellular uptake and lack of intracellular delivery represents major barriers for the widespread use of RNA interference, along with the instability of RNA at physiological conditions. This is due to unfavourable biopharmaceutical characteristics of the relatively large and polyanionic small interfering RNA duplexes. Therefore, successful clinical application depends on effective delivery systems to circumvent drug degradation and excretion, as well as to direct the small interfering RNAs towards the diseased tissue to reach the cytoplasm of the target cells. Non-viral, polymeric carriers are widely used delivery vehicles for nucleic acids in general. This review gives an overview of currently applied polymer-based nanoparticulate delivery systems for small interfering RNAs, with focus on the physico-chemical properties of the carriers and on reported in vivo applications. In addition, the safety of polymeric siRNA delivery system is discussed, and possible ways to overcome problems of toxicity and immune activation are highlighted.

Keywords: DELIVERY; IMMUNE ACTIVATION; NANOMEDICINE; NANOPARTICLES; POLYMERS; POLYPLEXES; RNA INTERFERENCE; SAFETY; SIRNA; TOXICITY

Document Type: Review Article

DOI: http://dx.doi.org/10.1166/jbn.2008.328

Publication date: September 1, 2008

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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