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Designing gene therapy vectors: avoiding immune responses by using tissue-specific promoters

Gene Therapy volume 8, pages 1872–1878 (2001)Cite this article

Abstract

Attempts to correct genetic disorders by gene therapy have been hindered by various problems including unwanted immune responses against the gene product. It has been shown that immune responses with DNA vaccines after i.m. injection of antigen-encoding plasmid DNA are primed solely by professional antigen-presenting cells (APC), even though myocytes are the primary type of cell transfected. This possibly involves direct transfection of some APC in regional lymph nodes draining the injected muscle. Here we have used plasmid DNA vaccines that express hepatitis B surface antigen (HBsAg) to evaluate the possibility of abrogating these immune responses by use of a tissue-specific promoter that does not drive expression in APC. We show that HBsAg-specific humoral or cell-mediated responses are not induced in mice when the muscle-specific human muscle creatine kinase promoter is used in place of the ubiquitous cytomegaloviral promoter to drive expression of HBsAg. This may have significance in the field of gene therapy where one aims to achieve stable expression of the desired gene product without interference from the host immune response.

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Acknowledgements

We are most grateful to Amanda Boyd, Lorraine Hamblin and Yu Xu for technical assistance. We also thank Dr Yubo Ren for his help with confocal microscopy and Dr Richard Bartlett for providing plasmids (see Materials and methods).

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Authors and Affiliations

  1. Coley Pharmaceutical Canada, Ottawa, ON, Canada

    RD Weeratna, SM Efler, L Zhang & HL Davis

  2. Loeb Health Research Institute at the Ottawa Hospital, Ottawa, Canada

    T Wu

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  1. RD Weeratna
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  2. T Wu
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  3. SM Efler
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Weeratna, R., Wu, T., Efler, S. et al. Designing gene therapy vectors: avoiding immune responses by using tissue-specific promoters. Gene Ther 8, 1872–1878 (2001). https://doi.org/10.1038/sj.gt.3301602

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