Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

Caitriona McLean*, Catherine M Greene*, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT...

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Autores principales:	Caitriona McLean, Catherine M Greene, Noel G McElvaney
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/03de50986b7b4813ac5ce3b18ebd77f0
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spelling	oai:doaj.org-article:03de50986b7b4813ac5ce3b18ebd77f02021-12-02T01:22:10ZGene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency1177-54751177-5491https://doaj.org/article/03de50986b7b4813ac5ce3b18ebd77f02009-01-01T00:00:00Zhttp://www.dovepress.com/gene-targeted-therapeutics-for-liver-disease-in-alpha-1-antitrypsin-de-a2813https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Caitriona McLean, Catherine M Greene, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to &lt;35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.Keywords: alpha-1 antitrypsin deficiency, siRNA, peptide nucleic acid, ribozymes Caitriona McLeanCatherine M GreeneNoel G McElvaneyDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2009, Iss default, Pp 63-75 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Caitriona McLean Catherine M Greene Noel G McElvaney Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
description	Caitriona McLean, Catherine M Greene, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to &lt;35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.Keywords: alpha-1 antitrypsin deficiency, siRNA, peptide nucleic acid, ribozymes
format	article
author	Caitriona McLean Catherine M Greene Noel G McElvaney
author_facet	Caitriona McLean Catherine M Greene Noel G McElvaney
author_sort	Caitriona McLean
title	Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
title_short	Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
title_full	Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
title_fullStr	Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
title_full_unstemmed	Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
title_sort	gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/03de50986b7b4813ac5ce3b18ebd77f0
work_keys_str_mv	AT caitrionamclean genetargetedtherapeuticsforliverdiseaseinalpha1antitrypsindeficiency AT catherinemgreene genetargetedtherapeuticsforliverdiseaseinalpha1antitrypsindeficiency AT noelgmcelvaney genetargetedtherapeuticsforliverdiseaseinalpha1antitrypsindeficiency
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Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

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