bioRxivJClub
Naked antisense oligonucleotides access the cytosol during early endocytic trafficking
bioRxiv · · Preprint · Open access
Sitarska, Saminathan + 12 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
In U2OS cells, less than 4% of internalized Malat1-targeting phosphorothioate ASO reached the nucleus, despite >90% Malat1 RNA reduction.
- Why it matters: The key uncertainty is where naked ASOs productively escape endocytic compartments to reach their RNA targets.
- What they did: Using live-cell imaging with ratiometric pH tracking, the study mapped ASO trafficking and tested escape by perturbing membranes (L-leucyl-L-leucine methyl ester, lysosome exocytosis) and endosomal recycling (tantalosin).
- The result: ASO foci neutralized luminal pH without membrane rupture or galectin-3 recruitment, and tantalosin enhanced early escape signals and Malat1 knockdown, implying productive escape occurs early in endocytic trafficking before late-compartment sequestration.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.
- Open access
- 1 cites