Optimization of an E1A Gene Expression Cassette in an Oncolytic Adenovirus for Efficient Tumor Cell Killing Activity.
Adenoviridae
/ genetics
Adenovirus E1A Proteins
/ genetics
Apoptosis
Cell Line, Tumor
Gene Expression
HCT116 Cells
HEK293 Cells
HeLa Cells
Hep G2 Cells
Human Umbilical Vein Endothelial Cells
Humans
MCF-7 Cells
Oncolytic Virotherapy
Oncolytic Viruses
/ genetics
Promoter Regions, Genetic
Sequence Deletion
Survivin
/ genetics
Telomerase
/ genetics
Virus Replication
E1A
Oncolytic adenovirus
expression cassette
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
31
12
2020
revised:
19
01
2021
accepted:
21
01
2021
entrez:
31
1
2021
pubmed:
1
2
2021
medline:
7
2
2021
Statut:
ppublish
Résumé
Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer therapeutics. The proper design of an expression cassette containing the E1A gene, which is indispensable for self-replication of the Ad genome, is crucial for efficient tumor cell-specific infection of an OAd. Various types of oncolytic adenoviruses (OAds) possessing different types of the E1A gene expression cassettes have been developed, but their oncolytic activities and safety profiles have not been systematically evaluated. Herein we examined the oncolytic activities and safety profiles of five types of OAds possessing different types of the E1A gene expression cassette in order to optimize the E1A gene expression cassette for development of an efficient and safe OAd. We prepared five types of OAds containing different types of E1 gene expression cassettes, and examined the oncolytic activities and safety profiles of the OAds. Among the OAds examined, OAd-Δ24, which had a 24-bp deletion in the E1A gene, mediated the most efficient oncolytic activities against the human tumor cell lines, although OAd-Δ24 showed slightly higher cytotoxicity to normal human cells than the other OAds. These results provide important clues for the development of safe and efficient OAds.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer therapeutics. The proper design of an expression cassette containing the E1A gene, which is indispensable for self-replication of the Ad genome, is crucial for efficient tumor cell-specific infection of an OAd. Various types of oncolytic adenoviruses (OAds) possessing different types of the E1A gene expression cassettes have been developed, but their oncolytic activities and safety profiles have not been systematically evaluated. Herein we examined the oncolytic activities and safety profiles of five types of OAds possessing different types of the E1A gene expression cassette in order to optimize the E1A gene expression cassette for development of an efficient and safe OAd.
MATERIALS AND METHODS
METHODS
We prepared five types of OAds containing different types of E1 gene expression cassettes, and examined the oncolytic activities and safety profiles of the OAds.
RESULTS
RESULTS
Among the OAds examined, OAd-Δ24, which had a 24-bp deletion in the E1A gene, mediated the most efficient oncolytic activities against the human tumor cell lines, although OAd-Δ24 showed slightly higher cytotoxicity to normal human cells than the other OAds.
CONCLUSION
CONCLUSIONS
These results provide important clues for the development of safe and efficient OAds.
Identifiants
pubmed: 33517282
pii: 41/2/773
doi: 10.21873/anticanres.14829
doi:
Substances chimiques
Adenovirus E1A Proteins
0
BIRC5 protein, human
0
Survivin
0
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
773-782Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.