Thursday, August 8, 2013
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pathways to enhance cellular retention of lipid nanoparticle (LNP)-delivered
small interfering RNAs
Inhibiting exocytosis of
LNP-delivered siRNAs from endosomes could enhance their retention within the
cell. In cultured cells, knockout of Niemann-Pick
disease type C1 (NPC1),
which encodes a protein important for endosome recycling, increased siRNA
accumulation and gene silencing compared with no knockout. In cells, genetic
depletion of other endosome recycling targets yielded comparable outcomes.
Next steps could include targeting proteins and lipids involved in biogenesis
and endosome trafficking to enhance cellular retention of LNP-delivered
Published online Aug. 8, 2013
Patent and licensing status
Sahay, G. et al. Nat.
Biotechnol.; published online June 23, 2013;
Contact: Daniel G. Anderson, Massachusetts Institute of
Technology, Cambridge, Mass.
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