Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein

Sivakumar Jeyarajan*, Jennifer Xavier*, N Madhusudhana Rao, Vijaya GopalCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Hyderabad, Andhra Pradesh, India; *These authors contributed equally to this workAbstract: A major rate-limiting step in nonviral gene de...

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Autores principales:	Sivakumar Jeyarajan, Jennifer Xavier, N Madhusudhana Rao, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d10649d76b1944679790f21da2675c95
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spelling	oai:doaj.org-article:d10649d76b1944679790f21da2675c952021-12-02T05:17:40ZPlasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein1176-91141178-2013https://doaj.org/article/d10649d76b1944679790f21da2675c952010-09-01T00:00:00Zhttp://www.dovepress.com/plasmid-dna-delivery-into-mda-mb-453-cells-mediated-by-recombinant-her-a5333https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Sivakumar Jeyarajan, Jennifer Xavier, N Madhusudhana Rao, Vijaya GopalCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Hyderabad, Andhra Pradesh, India; *These authors contributed equally to this workAbstract: A major rate-limiting step in nonviral gene delivery is the entry of nucleic acids across various membrane barriers and eventually into the nucleus where it must be transcribed. Cell-penetrating peptides and proteins are employed to generate formulations that overcome these challenges to facilitate DNA delivery into cells efficiently. However, these are limited by their inability to deliver nucleic acids selectively due to lack of specificity because they deliver to both cancer and normal cells. In this study, through modular design, we generated a recombinant fusion protein designated as Her-nuclear localization sequence (Her-NLS), where heregulin-a (Her), a targeting moiety, was cloned in frame with cationic NLS peptide to obtain a cell-specific targeting biomolecule for nucleic acid delivery. The heregulin-a1 isoform possesses the epidermal growth factor-like domain and binds to HER2/3 heterodimers which are overexpressed in certain breast cancers. Purified recombinant Her-NLS fusion protein binds plasmid DNA and specifically transfects MDA-MB-453 cells overexpressing the epidermal growth factor receptors HER2/3 in vitro. The approach described would also permit replacement of heregulin ligand with other targeting moieties that would be suited to cell-specific nucleic acid delivery mediated via receptor-ligand interactions.Keywords: cell targeting, nucleic acid delivery, nuclear localization sequences, heregulin, transfection, HER2 receptors Sivakumar JeyarajanJennifer XavierN Madhusudhana Raoet alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 725-733 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Sivakumar Jeyarajan Jennifer Xavier N Madhusudhana Rao et al Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
description	Sivakumar Jeyarajan, Jennifer Xavier, N Madhusudhana Rao, Vijaya GopalCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Hyderabad, Andhra Pradesh, India; *These authors contributed equally to this workAbstract: A major rate-limiting step in nonviral gene delivery is the entry of nucleic acids across various membrane barriers and eventually into the nucleus where it must be transcribed. Cell-penetrating peptides and proteins are employed to generate formulations that overcome these challenges to facilitate DNA delivery into cells efficiently. However, these are limited by their inability to deliver nucleic acids selectively due to lack of specificity because they deliver to both cancer and normal cells. In this study, through modular design, we generated a recombinant fusion protein designated as Her-nuclear localization sequence (Her-NLS), where heregulin-a (Her), a targeting moiety, was cloned in frame with cationic NLS peptide to obtain a cell-specific targeting biomolecule for nucleic acid delivery. The heregulin-a1 isoform possesses the epidermal growth factor-like domain and binds to HER2/3 heterodimers which are overexpressed in certain breast cancers. Purified recombinant Her-NLS fusion protein binds plasmid DNA and specifically transfects MDA-MB-453 cells overexpressing the epidermal growth factor receptors HER2/3 in vitro. The approach described would also permit replacement of heregulin ligand with other targeting moieties that would be suited to cell-specific nucleic acid delivery mediated via receptor-ligand interactions.Keywords: cell targeting, nucleic acid delivery, nuclear localization sequences, heregulin, transfection, HER2 receptors
format	article
author	Sivakumar Jeyarajan Jennifer Xavier N Madhusudhana Rao et al
author_facet	Sivakumar Jeyarajan Jennifer Xavier N Madhusudhana Rao et al
author_sort	Sivakumar Jeyarajan
title	Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
title_short	Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
title_full	Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
title_fullStr	Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
title_full_unstemmed	Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein
title_sort	plasmid dna delivery into mda-mb-453 cells mediated by recombinant her-nls fusion protein
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/d10649d76b1944679790f21da2675c95
work_keys_str_mv	AT sivakumarjeyarajan plasmiddnadeliveryintomdamb453cellsmediatedbyrecombinanthernlsfusionprotein AT jenniferxavier plasmiddnadeliveryintomdamb453cellsmediatedbyrecombinanthernlsfusionprotein AT nmadhusudhanarao plasmiddnadeliveryintomdamb453cellsmediatedbyrecombinanthernlsfusionprotein AT etal plasmiddnadeliveryintomdamb453cellsmediatedbyrecombinanthernlsfusionprotein
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Plasmid DNA delivery into MDA-MB-453 cells mediated by recombinant Her-NLS fusion protein

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