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Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells

A novel suicide gene therapy approach was tested in U87 MG glioblastoma multiforme cells. A 26nt G-rich double-stranded DNA aptamer (AS1411) was integrated into a vector at the 5′ of a mammalian codon-optimized saporin gene, under CMV promoter. With this plasmid termed “APTSAP”, the gene encoding ri...

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Detalles Bibliográficos
Autores principales: di Leandro, Luana, Giansanti, Francesco, Mei, Sabrina, Ponziani, Sara, Colasante, Martina, Ardini, Matteo, Angelucci, Francesco, Pitari, Giuseppina, d’Angelo, Michele, Cimini, Annamaria, Fabbrini, Maria Serena, Ippoliti, Rodolfo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082512/
https://www.ncbi.nlm.nih.gov/pubmed/33935695
http://dx.doi.org/10.3389/fphar.2021.588306
Descripción
Sumario:A novel suicide gene therapy approach was tested in U87 MG glioblastoma multiforme cells. A 26nt G-rich double-stranded DNA aptamer (AS1411) was integrated into a vector at the 5′ of a mammalian codon-optimized saporin gene, under CMV promoter. With this plasmid termed “APTSAP”, the gene encoding ribosome-inactivating protein saporin is driven intracellularly by the glioma-specific aptamer that binds to cell surface-exposed nucleolin and efficiently kills target cells, more effectively as a polyethyleneimine (PEI)-polyplex. Cells that do not expose nucleolin at the cell surface such as 3T3 cells, used as a control, remain unaffected. Suicide gene-induced cell killing was not observed when the inactive saporin mutant SAPKQ DNA was used in the (PEI)-polyplex, indicating that saporin catalytic activity mediates the cytotoxic effect. Rather than apoptosis, cell death has features resembling autophagic or methuosis-like mechanisms. These main findings support the proof-of-concept of using PEI-polyplexed APTSAP for local delivery in rat glioblastoma models.