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A major route of elimination of siRNA from the bloodstream is through kidney fil

ID: 255417 • Letter: A

Question

A major route of elimination of siRNA from the bloodstream is through kidney filtration. As naked siRNA can pass through the glomerular filtration barrier, 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

what is "are smaller than this cutoff" mean?

and why ?? how this happened?

Explanation / Answer

Cutoff is 20 nm, if bigger then this elimination of siRNA from the bloodstream will not happen. Mentioned delivery systems have size smaller then 20nm so they can load the siRNA onto them and reach the target site and deliver it there.

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