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- Title
Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells.
- Authors
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
- Abstract
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.
- Subjects
NUCLEOLIN; GLIOBLASTOMA multiforme; POLYETHYLENEIMINE; GENES; TOXINS; APTAMERS; RIBOSOMES
- Publication
Frontiers in Pharmacology, 2021, Vol 11, pN.PAG
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2021.588306