In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery - PubMed
a day ago
- #lipid nanoparticles
- #endosomal escape
- #CRISPR-Cas9
- Development of a library of branched ionizable phospholipids enhancing mRNA delivery to the liver.
- Lead candidate BiP-20 showed eightfold better performance than LP01 in CRISPR-Cas9 editing of the TTR gene.
- Utilization of LysoTag mice and Lysosomal Barcoding method to quantify endosomal escape kinetics (~8% of BiP-20 LNPs reach cytosol in 30 min).
- Lysosomal proteomics identified Rab7 as a regulator of LNP escape; loss of Rab7 increased escape efficiency.
- Provides insights into endolysosomal determinants of LNP trafficking and a method to quantify endosomal escape in vivo.