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A major route of elimination of siRNA from the bloodstream is through kidney filtration. As naked siRNA can pass through the glomerular filtration barrier99, many delivery systems prevent renal clearance by encapsulating siRNA into particles larger than ~20nm17. It should be noted that several highly efficacious delivery systems, including Dynamic PolyConjugates (DPCs)100 and triantennary N-acetylgalactosamine (GalNAc) conjugates101, are smaller than this cutoff, which probably reflects the fact that these delivery systems mainly deliver their payloads in the first pass through the liver. Some nanoparticulate systems undergo disassembly in the glomerulus102,103. Interaction with the negatively charged glomerular basement membrane can disrupt the electrostatic interactions that are essential to the stability of certain particles, which causes disassembly and passage of siRNA into urine102,10

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Sixta Kovacek
Sixta KovacekLv2
28 Sep 2019

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