caa a22 4500 445312599 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0608-1 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0608-1 Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA [Elektronische Daten] [Saurabh Singh, Ajit Narang, Ram Mahato] ABSTRACT: RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has the potential to selectively inhibit gene expression by degrading or blocking the translation of the target mRNA. However, delivering these RNAs to specific cells presents a significant challenge. Some of these challenges result from the necessity of traversing the circulatory system while avoiding kidney filtration, degradation by endonucleases, aggregation with serum proteins, and uptake by phagocytes. Further, non-specific delivery may result in side-effects, including the activation of immune response. We discuss the challenges in the systemic delivery to target cells, cellular uptake, endosomal release and intracellular transport of RNAi drugs and recent progress in overcoming these barriers. We also discuss approaches that increase the specificity and metabolic stability and reduce the off-target effects of RNAi strategy. Springer Science+Business Media, LLC, 2011 cellular uptake nationallicence intracellular trafficking nationallicence miRNA nationallicence RNA interference nationallicence shRNA nationallicence siRNA nationallicence Singh Saurabh Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 19 S Manassas, RM 224, 38103-3308, Memphis, Tennessee, USA aut Narang Ajit Bristol-Myers Squibb, Co., Biopharmaceutics R&D, 08901, New Brunswick, New Jersey, USA aut Mahato Ram Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 19 S Manassas, RM 224, 38103-3308, Memphis, Tennessee, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 2996-3015 0724-8741 28:12<2996 2011 28 11095 https://doi.org/10.1007/s11095-011-0608-1 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0608-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Singh Saurabh Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 19 S Manassas, RM 224, 38103-3308, Memphis, Tennessee, USA aut NATIONALLICENCE 700 1- Narang Ajit Bristol-Myers Squibb, Co., Biopharmaceutics R&D, 08901, New Brunswick, New Jersey, USA aut NATIONALLICENCE 700 1- Mahato Ram Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 19 S Manassas, RM 224, 38103-3308, Memphis, Tennessee, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 2996-3015 0724-8741 28:12<2996 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer