No immune responses by the expression of the yeast Ndi1 protein in rats
Document TypeJournal Article
KeywordsSaccharomyces cerevisiae Proteins
Electron Transport Complex I
Allergy and Immunology
Genetics and Genomics
Immunology and Infectious Disease
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AbstractBACKGROUND: The rotenone-insensitive internal NADH-quinone oxidoreductase from yeast, Ndi1, has been shown to work as a replacement molecule for complex I in the respiratory chain of mammalian mitochondria. In the so-called transkingdom gene therapy, one major concern is the fact that the yeast protein is foreign in mammals. Long term expression of Ndi1 observed in rodents with no apparent damage to the target tissue was indicative of no action by the host's immune system. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we examined rat skeletal muscles expressing Ndi1 for possible signs of inflammatory or immune response. In parallel, we carried out delivery of the GFP gene using the same viral vector that was used for the NDI1 gene. The tissues were subjected to H&E staining and immunohistochemical analyses using antibodies specific for markers, CD11b, CD3, CD4, and CD8. The data showed no detectable signs of an immune response with the tissues expressing Ndi1. In contrast, mild but distinctive positive reactions were observed in the tissues expressing GFP. This clear difference most likely comes from the difference in the location of the expressed protein. Ndi1 was localized to the mitochondria whereas GFP was in the cytosol. CONCLUSIONS/SIGNIFICANCE: We demonstrated that Ndi1 expression did not trigger any inflammatory or immune response in rats. These results push forward the Ndi1-based molecular therapy and also expand the possibility of using foreign proteins that are directed to subcellular organelle such as mitochondria.
SourceMarella M, Seo BB, Flotte TR, Matsuno-Yagi A, Yagi T (2011) No Immune Responses by the Expression of the Yeast Ndi1 Protein in Rats. PLoS ONE 6(10): e25910. doi:10.1371/journal.pone.0025910. Link to article on publisher's website
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43850
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Copyright: © 2011 Marella et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.