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Abstract
The enormous promise of siRNA technology for rational and targeted therapy can only be realized if the inherent problems in terms of pharmaceutical development are overcome. Besides liposomal and polymeric nanoparticles, fusion proteins hold great potential for cell-type specific delivery of siRNA. Consisting of a protein binder and an oligonucleotide complexing domain, fusion proteins are designed for targeted delivery to a certain tissue or organ and subsequent release of the siRNA after cellular uptake. This article focuses on the possibilities and importance of targeting and complexing domains, including polymers and dendrimers. In vitro and in vivo evaluations are discussed with an in-depth view on pharmacokinetic properties. Remaining challenges concerning specificity on the tissue and molecular levels are highlighted.
Acknowledgements
The author thanks Martina Stessl for critical reading of the manuscript.
Financial & competing interests disclosure
Work of the author is supported by the Austrian Science Fund (FWF): J2593-B11 and I519-B11. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.