Novel method to load multiple genes onto a mammalian artificial chromosome.

Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier de...

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Autores principales:	Anna Tóth, Katalin Fodor, Tünde Praznovszky, Vilmos Tubak, Andor Udvardy, Gyula Hadlaczky, Robert L Katona
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f4273f10e4a3495b9e5d460d1935b20b
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spelling	oai:doaj.org-article:f4273f10e4a3495b9e5d460d1935b20b2021-11-18T08:37:39ZNovel method to load multiple genes onto a mammalian artificial chromosome.1932-620310.1371/journal.pone.0085565https://doaj.org/article/f4273f10e4a3495b9e5d460d1935b20b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24454889/?tool=EBIhttps://doaj.org/toc/1932-6203Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.Anna TóthKatalin FodorTünde PraznovszkyVilmos TubakAndor UdvardyGyula HadlaczkyRobert L KatonaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85565 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Tóth Katalin Fodor Tünde Praznovszky Vilmos Tubak Andor Udvardy Gyula Hadlaczky Robert L Katona Novel method to load multiple genes onto a mammalian artificial chromosome.
description	Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.
format	article
author	Anna Tóth Katalin Fodor Tünde Praznovszky Vilmos Tubak Andor Udvardy Gyula Hadlaczky Robert L Katona
author_facet	Anna Tóth Katalin Fodor Tünde Praznovszky Vilmos Tubak Andor Udvardy Gyula Hadlaczky Robert L Katona
author_sort	Anna Tóth
title	Novel method to load multiple genes onto a mammalian artificial chromosome.
title_short	Novel method to load multiple genes onto a mammalian artificial chromosome.
title_full	Novel method to load multiple genes onto a mammalian artificial chromosome.
title_fullStr	Novel method to load multiple genes onto a mammalian artificial chromosome.
title_full_unstemmed	Novel method to load multiple genes onto a mammalian artificial chromosome.
title_sort	novel method to load multiple genes onto a mammalian artificial chromosome.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f4273f10e4a3495b9e5d460d1935b20b
work_keys_str_mv	AT annatoth novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT katalinfodor novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT tundepraznovszky novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT vilmostubak novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT andorudvardy novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT gyulahadlaczky novelmethodtoloadmultiplegenesontoamammalianartificialchromosome AT robertlkatona novelmethodtoloadmultiplegenesontoamammalianartificialchromosome
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Novel method to load multiple genes onto a mammalian artificial chromosome.

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