Regulation of transgene expression in genetic immunization

The use of mammalian gene expression vectors has become increasingly important for genetic immunization and gene therapy as well as basic research. Essential for the success of these vectors in genetic immunization is the proper choice of a promoter linked to the antigen of interest. Many genetic im...

Full description

Bibliographic Details
Main Authors: Harms J.S., Oliveira S.C., Splitter G.A.
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 1999-01-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1999000200003
_version_ 1819038506628939776
author Harms J.S.
Oliveira S.C.
Splitter G.A.
author_facet Harms J.S.
Oliveira S.C.
Splitter G.A.
author_sort Harms J.S.
collection DOAJ
description The use of mammalian gene expression vectors has become increasingly important for genetic immunization and gene therapy as well as basic research. Essential for the success of these vectors in genetic immunization is the proper choice of a promoter linked to the antigen of interest. Many genetic immunization vectors use promoter elements from pathogenic viruses including SV40 and CMV. Lymphokines produced by the immune response to proteins expressed by these vectors could inhibit further transcription initiation by viral promoters. Our objective was to determine the effect of IFN-<FONT FACE="Symbol">g</FONT> on transgene expression driven by viral SV40 or CMV promoter/enhancer and the mammalian promoter/enhancer for the major histocompatibility complex class I (MHC I) gene. We transfected the luciferase gene driven by these three promoters into 14 cell lines of many tissues and several species. Luciferase assays of transfected cells untreated or treated with IFN-<FONT FACE="Symbol">g</FONT> indicated that although the viral promoters could drive luciferase production in all cell lines tested to higher or lower levels than the MHC I promoter, treatment with IFN-<FONT FACE="Symbol">g</FONT> inhibited transgene expression in most of the cell lines and amplification of the MHC I promoter-driven transgene expression in all cell lines. These data indicate that the SV40 and CMV promoter/enhancers may not be a suitable choice for gene delivery especially for genetic immunization or cancer cytokine gene therapy. The MHC I promoter/enhancer, on the other hand, may be an ideal transgene promoter for applications involving the immune system.
first_indexed 2024-12-21T08:38:24Z
format Article
id doaj.art-2f996d2f9fa9410a8edd6572f1cccc15
institution Directory Open Access Journal
issn 0100-879X
0034-7310
language English
last_indexed 2024-12-21T08:38:24Z
publishDate 1999-01-01
publisher Associação Brasileira de Divulgação Científica
record_format Article
series Brazilian Journal of Medical and Biological Research
spelling doaj.art-2f996d2f9fa9410a8edd6572f1cccc152022-12-21T19:10:01ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X0034-73101999-01-01322Regulation of transgene expression in genetic immunizationHarms J.S.Oliveira S.C.Splitter G.A.The use of mammalian gene expression vectors has become increasingly important for genetic immunization and gene therapy as well as basic research. Essential for the success of these vectors in genetic immunization is the proper choice of a promoter linked to the antigen of interest. Many genetic immunization vectors use promoter elements from pathogenic viruses including SV40 and CMV. Lymphokines produced by the immune response to proteins expressed by these vectors could inhibit further transcription initiation by viral promoters. Our objective was to determine the effect of IFN-<FONT FACE="Symbol">g</FONT> on transgene expression driven by viral SV40 or CMV promoter/enhancer and the mammalian promoter/enhancer for the major histocompatibility complex class I (MHC I) gene. We transfected the luciferase gene driven by these three promoters into 14 cell lines of many tissues and several species. Luciferase assays of transfected cells untreated or treated with IFN-<FONT FACE="Symbol">g</FONT> indicated that although the viral promoters could drive luciferase production in all cell lines tested to higher or lower levels than the MHC I promoter, treatment with IFN-<FONT FACE="Symbol">g</FONT> inhibited transgene expression in most of the cell lines and amplification of the MHC I promoter-driven transgene expression in all cell lines. These data indicate that the SV40 and CMV promoter/enhancers may not be a suitable choice for gene delivery especially for genetic immunization or cancer cytokine gene therapy. The MHC I promoter/enhancer, on the other hand, may be an ideal transgene promoter for applications involving the immune system.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1999000200003DNA vaccinegene therapyregulationtranscriptiontransgene
spellingShingle Harms J.S.
Oliveira S.C.
Splitter G.A.
Regulation of transgene expression in genetic immunization
Brazilian Journal of Medical and Biological Research
DNA vaccine
gene therapy
regulation
transcription
transgene
title Regulation of transgene expression in genetic immunization
title_full Regulation of transgene expression in genetic immunization
title_fullStr Regulation of transgene expression in genetic immunization
title_full_unstemmed Regulation of transgene expression in genetic immunization
title_short Regulation of transgene expression in genetic immunization
title_sort regulation of transgene expression in genetic immunization
topic DNA vaccine
gene therapy
regulation
transcription
transgene
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1999000200003
work_keys_str_mv AT harmsjs regulationoftransgeneexpressioningeneticimmunization
AT oliveirasc regulationoftransgeneexpressioningeneticimmunization
AT splitterga regulationoftransgeneexpressioningeneticimmunization