SiRNA-conjugate delivery systems

Jeong JH, Mok H, Oh YK, Park TG. siRNA conjugate delivery systems. Bioconjug. Chem. 2009 20 5-14. 

Fig. 7 Schematic diagram of the cyclodextrin-containing delivery system, (a) Components of the delivery system. The CDP condenses siRNA and protects it from degradation. The AD-PEG stabilizes the complexes in systemic circulation via inclusion compound formation. The AD-PEG-transferrin (Tf-PEG-AD) conjugate confers a targeting ligand to the complex, (b) Assembly of the targeted delivery systems. CDP, AD-PEG, and Tf-PEG-AD are combined and added to siRNA to generate stable complex. (Adopted from Cancer Research 2005 65 8984-8992)...

This chapter broadly describes the lead optimization activities relevant to the development of novel conjugate siRNA therapeutics for hepatic targets via subcutaneous administration. For specific information regarding other therapeutic oligonucleotide technologies (e.g., antisense, aptamer, CpG, anti-miR), specific nanoparticle-based delivery systems, or non-hepatic targeting, readers are directed elsewhere (Bennett and Swayze, 2010 Kole et al., 2012). 

S. H. Lee, S. H. Kim and T. G. Park, Intracellular siRNA delivery system using polyelectrolyte complex micelles prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide. 

Despite the overall success with lipid and polymeric-based nucleic acid delivery, it has been conceptualized that simpler systems may achieve similar results in terms of delivery and knockdown efficacy. As such, siRNA-conjugates are being explored as therapeutic platforms. 

Tremendous efforts have been made to overcome these challenges, cationic liposome and positively charged polymers are currently being used as the most common method to complex with negatively charged siRNA for systemic delivery [30, 36]. Other in vivo delivery approaches include conjugation with cholesterol, aptamer, peptide complexation with antibody-protamine fusion protein or encapsulation in cyclodextrin nanoparticles [35, 37-39]. 

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