Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500002 |
Resumo: | A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence. |
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Brazilian Journal of Medical and Biological Research |
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Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiencyRetrovirusInsertional mutagenesisSevere combined immune deficiencyGene therapyAdverse eventClinical trialA successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.Associação Brasileira de Divulgação Científica2007-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500002Brazilian Journal of Medical and Biological Research v.40 n.5 2007reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/S0100-879X2006005000085info:eu-repo/semantics/openAccessStrauss,B.E.Costanzi-Strauss,E.eng2008-02-12T00:00:00Zoai:scielo:S0100-879X2007000500002Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2008-02-12T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
title |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
spellingShingle |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency Strauss,B.E. Retrovirus Insertional mutagenesis Severe combined immune deficiency Gene therapy Adverse event Clinical trial |
title_short |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
title_full |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
title_fullStr |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
title_full_unstemmed |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
title_sort |
Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency |
author |
Strauss,B.E. |
author_facet |
Strauss,B.E. Costanzi-Strauss,E. |
author_role |
author |
author2 |
Costanzi-Strauss,E. |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Strauss,B.E. Costanzi-Strauss,E. |
dc.subject.por.fl_str_mv |
Retrovirus Insertional mutagenesis Severe combined immune deficiency Gene therapy Adverse event Clinical trial |
topic |
Retrovirus Insertional mutagenesis Severe combined immune deficiency Gene therapy Adverse event Clinical trial |
description |
A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-05-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500002 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500002 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0100-879X2006005000085 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.40 n.5 2007 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
_version_ |
1754302935904288768 |