Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells.
AS1411 aptamer
DNA-based gene delivery
glioblastoma
nucleolin
saporin
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
10
2020
accepted:
16
03
2021
entrez:
3
5
2021
pubmed:
4
5
2021
medline:
4
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33935695
doi: 10.3389/fphar.2021.588306
pii: 588306
pmc: PMC8082512
doi:
Types de publication
Journal Article
Langues
eng
Pagination
588306Informations de copyright
Copyright © 2021 di Leandro, Giansanti, Mei, Ponziani, Colasante, Ardini, Angelucci, Pitari, d’Angelo, Cimini, Fabbrini and Ippoliti.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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