Delivery of large transgene cassettes by foamy virus vector

Abstract Viral vectors are effective tools in gene therapy, but their limited packaging capacity can be restrictive. Larger clinically-relevant vectors are needed. Foamy viruses have the largest genomes among mammalian retroviruses and their vectors have shown potential for gene therapy in preclinic...

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Autores principales:	Nathan Paul Sweeney, Jinhong Meng, Hayley Patterson, Jennifer E. Morgan, Myra McClure
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a26dc39854a54893898e2bcd915a211e
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spelling	oai:doaj.org-article:a26dc39854a54893898e2bcd915a211e2021-12-02T11:52:37ZDelivery of large transgene cassettes by foamy virus vector10.1038/s41598-017-08312-32045-2322https://doaj.org/article/a26dc39854a54893898e2bcd915a211e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08312-3https://doaj.org/toc/2045-2322Abstract Viral vectors are effective tools in gene therapy, but their limited packaging capacity can be restrictive. Larger clinically-relevant vectors are needed. Foamy viruses have the largest genomes among mammalian retroviruses and their vectors have shown potential for gene therapy in preclinical studies. However, the effect of vector genome size on titre has not been determined. We inserted increasing lengths of the dystrophin open reading frame in a foamy virus vector and quantified packaged vector RNA and integrated DNA. For both measures, a semi-logarithmic reduction in titre was observed as genome size increased. Concentrated titres were reduced 100-fold to approximately 106 transducing units per ml when vector genomes harboured a 12 kb insert, approximately twice that reported for lentivirus vectors in a comparable study. This potential was applied by optimising foamy virus vectors carrying the full-length dystrophin open-reading frame for transduction of human muscle derived cells. Full-length dystrophin protein was expressed and transduced cells remained able to form myotubes in vitro. Foamy virus vectors are well-suited for stable delivery of large transgene cassettes and warrant further investigation for development as a therapy for Duchenne or Becker muscular dystrophy.Nathan Paul SweeneyJinhong MengHayley PattersonJennifer E. MorganMyra McClureNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathan Paul Sweeney Jinhong Meng Hayley Patterson Jennifer E. Morgan Myra McClure Delivery of large transgene cassettes by foamy virus vector
description	Abstract Viral vectors are effective tools in gene therapy, but their limited packaging capacity can be restrictive. Larger clinically-relevant vectors are needed. Foamy viruses have the largest genomes among mammalian retroviruses and their vectors have shown potential for gene therapy in preclinical studies. However, the effect of vector genome size on titre has not been determined. We inserted increasing lengths of the dystrophin open reading frame in a foamy virus vector and quantified packaged vector RNA and integrated DNA. For both measures, a semi-logarithmic reduction in titre was observed as genome size increased. Concentrated titres were reduced 100-fold to approximately 106 transducing units per ml when vector genomes harboured a 12 kb insert, approximately twice that reported for lentivirus vectors in a comparable study. This potential was applied by optimising foamy virus vectors carrying the full-length dystrophin open-reading frame for transduction of human muscle derived cells. Full-length dystrophin protein was expressed and transduced cells remained able to form myotubes in vitro. Foamy virus vectors are well-suited for stable delivery of large transgene cassettes and warrant further investigation for development as a therapy for Duchenne or Becker muscular dystrophy.
format	article
author	Nathan Paul Sweeney Jinhong Meng Hayley Patterson Jennifer E. Morgan Myra McClure
author_facet	Nathan Paul Sweeney Jinhong Meng Hayley Patterson Jennifer E. Morgan Myra McClure
author_sort	Nathan Paul Sweeney
title	Delivery of large transgene cassettes by foamy virus vector
title_short	Delivery of large transgene cassettes by foamy virus vector
title_full	Delivery of large transgene cassettes by foamy virus vector
title_fullStr	Delivery of large transgene cassettes by foamy virus vector
title_full_unstemmed	Delivery of large transgene cassettes by foamy virus vector
title_sort	delivery of large transgene cassettes by foamy virus vector
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a26dc39854a54893898e2bcd915a211e
work_keys_str_mv	AT nathanpaulsweeney deliveryoflargetransgenecassettesbyfoamyvirusvector AT jinhongmeng deliveryoflargetransgenecassettesbyfoamyvirusvector AT hayleypatterson deliveryoflargetransgenecassettesbyfoamyvirusvector AT jenniferemorgan deliveryoflargetransgenecassettesbyfoamyvirusvector AT myramcclure deliveryoflargetransgenecassettesbyfoamyvirusvector
_version_	1718395001479626752

Delivery of large transgene cassettes by foamy virus vector

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