A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy

Gene therapy is a promising strategy to cure rare diseases. The lack of regulatory sequences ensuring specific and robust expression in skeletal and cardiac muscle is a substantial limitation of gene therapy efficiency targeting the muscle tissue. Here we describe a novel muscle hybrid (MH) promoter...

Full description

Bibliographic Details
Main Authors:	Katarzyna Piekarowicz, Anne T. Bertrand, Feriel Azibani, Maud Beuvin, Laura Julien, Magdalena Machowska, Gisèle Bonne, Ryszard Rzepecki
Format:	Article
Language:	English
Published:	Elsevier 2019-12-01
Series:	Molecular Therapy: Methods & Clinical Development
Online Access:	http://www.sciencedirect.com/science/article/pii/S2329050119300981

id	doaj-d0332b0722974fadb605a4b15c9ce05f
record_format	Article
spelling	doaj-d0332b0722974fadb605a4b15c9ce05f2020-11-25T02:07:41ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012019-12-0115157169A Muscle Hybrid Promoter as a Novel Tool for Gene TherapyKatarzyna Piekarowicz0Anne T. Bertrand1Feriel Azibani2Maud Beuvin3Laura Julien4Magdalena Machowska5Gisèle Bonne6Ryszard Rzepecki7Laboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Wroclaw 50-383, PolandSorbonne Université, INSERM UMRS974, Center of Research in Myology, Institute of Myology, Paris 75 651, FranceSorbonne Université, INSERM UMRS974, Center of Research in Myology, Institute of Myology, Paris 75 651, FranceSorbonne Université, INSERM UMRS974, Center of Research in Myology, Institute of Myology, Paris 75 651, FranceSorbonne Université, INSERM UMRS974, Center of Research in Myology, Institute of Myology, Paris 75 651, FranceLaboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Wroclaw 50-383, PolandSorbonne Université, INSERM UMRS974, Center of Research in Myology, Institute of Myology, Paris 75 651, FranceLaboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Wroclaw 50-383, Poland; Corresponding author: Ryszard Rzepecki, Laboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Wroclaw 50-383, Poland.Gene therapy is a promising strategy to cure rare diseases. The lack of regulatory sequences ensuring specific and robust expression in skeletal and cardiac muscle is a substantial limitation of gene therapy efficiency targeting the muscle tissue. Here we describe a novel muscle hybrid (MH) promoter that is highly active in both skeletal and cardiac muscle cells. It has an easily exchangeable modular structure, including an intronic module that highly enhances the expression of the gene driven by it. In cultured myoblasts, myotubes, and cardiomyocytes, the MH promoter gives relatively stable expression as well as higher activity and protein levels than the standard CMV and desmin gene promoters or the previously developed synthetic or CKM-based promoters. Combined with AAV2/9, the MH promoter also provides a high in vivo expression level in skeletal muscle and the heart after both intramuscular and systemic delivery. It is much more efficient than the desmin-encoding gene promoter, and it maintains the same specificity. This novel promoter has potential for gene therapy in muscle cells. It can provide stable transgene expression, ensuring high levels of therapeutic protein, and limited side effects because of its specificity. This constitutes an improvement in the efficiency of genetic disease therapy. Keywords: muscle promoter, expression cassette, AAV, vector, skeletal muscles, heart, C2C12, myotubeshttp://www.sciencedirect.com/science/article/pii/S2329050119300981
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Katarzyna Piekarowicz Anne T. Bertrand Feriel Azibani Maud Beuvin Laura Julien Magdalena Machowska Gisèle Bonne Ryszard Rzepecki
spellingShingle	Katarzyna Piekarowicz Anne T. Bertrand Feriel Azibani Maud Beuvin Laura Julien Magdalena Machowska Gisèle Bonne Ryszard Rzepecki A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy Molecular Therapy: Methods & Clinical Development
author_facet	Katarzyna Piekarowicz Anne T. Bertrand Feriel Azibani Maud Beuvin Laura Julien Magdalena Machowska Gisèle Bonne Ryszard Rzepecki
author_sort	Katarzyna Piekarowicz
title	A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy
title_short	A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy
title_full	A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy
title_fullStr	A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy
title_full_unstemmed	A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy
title_sort	muscle hybrid promoter as a novel tool for gene therapy
publisher	Elsevier
series	Molecular Therapy: Methods & Clinical Development
issn	2329-0501
publishDate	2019-12-01
description	Gene therapy is a promising strategy to cure rare diseases. The lack of regulatory sequences ensuring specific and robust expression in skeletal and cardiac muscle is a substantial limitation of gene therapy efficiency targeting the muscle tissue. Here we describe a novel muscle hybrid (MH) promoter that is highly active in both skeletal and cardiac muscle cells. It has an easily exchangeable modular structure, including an intronic module that highly enhances the expression of the gene driven by it. In cultured myoblasts, myotubes, and cardiomyocytes, the MH promoter gives relatively stable expression as well as higher activity and protein levels than the standard CMV and desmin gene promoters or the previously developed synthetic or CKM-based promoters. Combined with AAV2/9, the MH promoter also provides a high in vivo expression level in skeletal muscle and the heart after both intramuscular and systemic delivery. It is much more efficient than the desmin-encoding gene promoter, and it maintains the same specificity. This novel promoter has potential for gene therapy in muscle cells. It can provide stable transgene expression, ensuring high levels of therapeutic protein, and limited side effects because of its specificity. This constitutes an improvement in the efficiency of genetic disease therapy. Keywords: muscle promoter, expression cassette, AAV, vector, skeletal muscles, heart, C2C12, myotubes
url	http://www.sciencedirect.com/science/article/pii/S2329050119300981
work_keys_str_mv	AT katarzynapiekarowicz amusclehybridpromoterasanoveltoolforgenetherapy AT annetbertrand amusclehybridpromoterasanoveltoolforgenetherapy AT ferielazibani amusclehybridpromoterasanoveltoolforgenetherapy AT maudbeuvin amusclehybridpromoterasanoveltoolforgenetherapy AT laurajulien amusclehybridpromoterasanoveltoolforgenetherapy AT magdalenamachowska amusclehybridpromoterasanoveltoolforgenetherapy AT giselebonne amusclehybridpromoterasanoveltoolforgenetherapy AT ryszardrzepecki amusclehybridpromoterasanoveltoolforgenetherapy AT katarzynapiekarowicz musclehybridpromoterasanoveltoolforgenetherapy AT annetbertrand musclehybridpromoterasanoveltoolforgenetherapy AT ferielazibani musclehybridpromoterasanoveltoolforgenetherapy AT maudbeuvin musclehybridpromoterasanoveltoolforgenetherapy AT laurajulien musclehybridpromoterasanoveltoolforgenetherapy AT magdalenamachowska musclehybridpromoterasanoveltoolforgenetherapy AT giselebonne musclehybridpromoterasanoveltoolforgenetherapy AT ryszardrzepecki musclehybridpromoterasanoveltoolforgenetherapy
_version_	1724930330803044352

A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy

Similar Items