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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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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
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author 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
author_facet 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
author_sort di Leandro, Luana
collection PubMed
description 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.
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spelling pubmed-80825122021-04-30 Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells 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 Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8082512/ /pubmed/33935695 http://dx.doi.org/10.3389/fphar.2021.588306 Text en Copyright © 2021 di Leandro, Giansanti, Mei, Ponziani, Colasante, Ardini, Angelucci, Pitari, d’Angelo, Cimini, Fabbrini and Ippoliti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
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
Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title_full Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title_fullStr Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title_full_unstemmed Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title_short Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells
title_sort aptamer-driven toxin gene delivery in u87 model glioblastoma cells
topic Pharmacology
url 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
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