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Abstract
Essence
A branched ionizable phospholipid LNP improved liver RNA delivery, and an in vivo assay linked stronger performance to faster endosomal escape and altered endolysosomal trafficking.
Evidence
This preclinical liver-delivery study developed branched ionizable phospholipids and used LysoTag mice plus lysosomal barcoding to show that the lead BiP-20 LNP outperformed LP01 eightfold for low-dose TTR gene editing and that about 8% of BiP-20 LNPs reached the cytosol within 30 minutes, alongside proteomic and Rab7-loss mechanistic findings.
Caveat
The results come from mouse delivery and mechanistic endosomal-trafficking experiments, so the hepatic editing advantage and escape mechanisms remain preclinical.
Simplified
CRISPR Gene Editing