?bution through a circulatory system in a f... From the bloodstream, siRNA will

Question

?bution through a circulatory system in a f...

From the bloodstream, siRNA will undergo initial distribution through a circulatory system in a few minutes. siRNA undergoes certain pathways to get eliminated from blood. It will get accumulated in the liver and through renal filtration and finally it will be excluded through urine. Many delivery systems blocks the passage of siRNA through kidneys by enfolding in to larger particles of size 20 nm17. Glomerular basement membrane (GBM) is the main component of renal filtration barrier. GBM causes disassembly of catatonic cyclodextrin containing polymer based siRNA nanoparticles, thereby facilitating rapid elimination of siRNA from circulation. siRNA generally assembled by electrostatic interactions between catatonic delivery components but that will be disturbed by GBM ( when siRNA binds with negativity charged GBM) since siRNA normally accumulate in GBM.

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Explanation / Answer

A major route of elimination of siRNA from blood stream is through kidney filtration.

siRNA can pass through the glomerular filtration barrier 99.

Several systems prevents renal clearance of siRNA into particles larger than ~20nm17. It should be noted that several highly efficacious delivery systems including DPCs 100 & GalNAc 101 probably reflects these delivery system (mainly through liver).

Some nanoparticulate system undergo disassembly in the glomerular 102,103.

Interaction of siRNA with negatively charged GBM can disrupt the electrostatic interactions. It leads to unstability of of certain particles, which causes disassembly and passage of siRNA into urine 102,10.

when the siRNA binds to negatively charged GBM that structurally mimic the polyanionic charge of nucleic acids, after disassembly, their components are small enough to cross GBM into urinary space.

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