ArticleMolecular therapy. Advances2026
Intracellular trafficking and nuclear compartmentalization of AAV gene delivery.
Article in Molecular therapy. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Recombinant adeno-associated virus (rAAV) capsids are widely used as therapeutic gene delivery vectors. The cellular trafficking pathway utilized by AAVs to transport the therapeutic gene to the nucleus and within the different nuclear compartments is still not clearly defined. This study maps the timeline and spatial trajectory of rAAV2-GFP (capsid packages a transgene that encodes GFP), AAV2-EMPTIES, and AAV2 variants during trafficking, over a 72-h time course using cellular cytoplasmic and nuclear markers by confocal microscopy and image analysis in fixed HeLa cells. This comparative spatiotemporal movement of rAAV2-GFP versus the AAV2-EMPTIES or AAV2 variants was shown to differ in cytoplasmic accumulation, late endosome association, transportation via actin and microtubule filaments, perinuclear accumulation, nuclear penetration, euchromatin, and heterochromatin regions of nucleus. The results demonstrate that rAAV2-GFP capsids were internalized into the cell within 2 hours; they utilized both actin and tubulin for transportation, penetrated the nucleus, and expressed the packaged GFP transgene. This is different from the trafficking profile exhibited by the AAV2-EMPTIES and AAV2 variants that were inhibited from entering the nucleus (except for AAV2-E563A). These data provide detailed insights into the trafficking of AAV both in the cytoplasm and the nucleus where it delivers its packaged transgene.
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