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Use of human MAR elements to improve retroviral vector production

Gene Therapy volume 18, pages 7–13 (2011)Cite this article

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Abstract

Retroviral vectors have many favorable properties for gene therapies, but their use remains limited by safety concerns and/or by relatively lower titers for some of the safer self-inactivating (SIN) derivatives. In this study, we evaluated whether increased production of SIN retroviral vectors can be achieved from the use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of human origin were found to increase and to stabilize the expression of the green fluorescent protein transgene in stably transfected HEK-293 packaging cells. Introduction of one of these MAR elements in retroviral vector-producing plasmids yielded higher expression of the viral vector RNA. Consistently, viral titers obtained from transient transfection of MAR-containing plasmids were increased up to sixfold as compared with the parental construct, when evaluated in different packaging cell systems and transfection conditions. Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors.

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Acknowledgements

We thank Dr Odile Cohen-Haguenauer for comments and improvements on the paper. This work was supported by grants from the Network of Excellence in Gene therapy (CLINIGENE-NOE) LSHB-CT-2006-018933 of the European FP6 program, the Swiss Commission for Technology and Innovation, Selexis SA, and by the Etat de Vaud.

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Author notes

  1. M Buceta

    Present address: 3Current address: Selexis SA, 18 Ch. des Aulx, Geneva, Switzerland.,

  2. M Buceta and J L Galbete: These authors contributed equally to this work.

Authors and Affiliations

  1. Faculty of Biology and Medicine, Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland

    M Buceta, J L Galbete & N Mermod

  2. Unit of Gene Therapy and Stem Cell Biology, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland

    C Kostic & Y Arsenijevic

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  1. M Buceta
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Correspondence to N Mermod.

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Competing interests

Dr Buceta's work was funded by a European Network of Excellence and by Selexis SA, and she has obtained an employment at this company after the completion of this work. Dr Mermod is a cofounder and owns stocks of the company. Dr Kostic and Dr Arsenijevic declare no potential conflict of interest.

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Buceta, M., Galbete, J., Kostic, C. et al. Use of human MAR elements to improve retroviral vector production. Gene Ther 18, 7–13 (2011). https://doi.org/10.1038/gt.2010.115

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