Enhanced Targeted Gene Transduction: AAV2 Vectors Conjugated to Multiple Aptamers via Reducible Disulfide Linkages.
Yuan WuLiqin ZhangCheng CuiSena CansizHao LiangCuichen WuI-Ting TengWeijun ChenYuan LiuWeijia HouXiao-Bing ZhangWeihong TanPublished in: Journal of the American Chemical Society (2017)
Enhanced targeted gene transduction by AAV2 vectors is achieved by linking the vector to multiple sgc8 aptamers, which are selective for cell membrane protein PTK7. Aptamer molecules are conjugated to multiple sites on a DNA dendrimer (G-sgc8), which is then linked to AAV2 via a dithiobis(succinimidyl propionate) cross-linker containing a disulfide group, which can facilitate the release of AAV2 vectors by reaction with the reduced form of intracellular glutathione. The G-sgc8-AAV2 vectors showed a 21-fold enhancement in binding affinity and an enhanced ability to protect sgc8 aptamers against nuclease degradation to cells expressing PTK7 compared to single aptamer-AAV2 conjugates. The transduction efficiency was tested by loading AAV2 with the gene for green fluorescent protein. Therefore, this modified recombinant vector is an attractive and promising tool for targeted biomedical applications.
Keyphrases
- gene therapy
- cancer therapy
- copy number
- genome wide
- gold nanoparticles
- induced apoptosis
- photodynamic therapy
- genome wide identification
- dna methylation
- mesenchymal stem cells
- cell proliferation
- mass spectrometry
- sensitive detection
- quantum dots
- cell therapy
- gene expression
- binding protein
- drug delivery
- reactive oxygen species
- signaling pathway
- endoplasmic reticulum stress
- living cells