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Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

Gene Therapy volume 19, pages 70–77 (2012)Cite this article

Abstract

The demonstration that naked plasmid DNA can induce strong immune responses in mice has attracted considerable attention in the vaccine community. However, similar immunizations have been less/not effective in clinical trials during the past decade, and the underlying mechanisms remain unknown. In this study, we hypothesized that some DNA-binding proteins in human serum may serve as host barriers, responsible for the low efficiency of plasmids’ transfection in vivo. Using proteomics, we showed that human serum amyloid P component (hSAP) is specifically present in human DNA–protein complexes. Further analysis indicated that hSAP effectively binds plasmid DNA, inhibits DNA transfection into somatic cells and facilitates the endocytosis of DNA by macrophages, whereas mouse SAP (mSAP) has similar, but much weaker, activities. In the presence of hSAP, the plasmid DNA expression in vivo and plasmid DNA-induced immune responses also significantly decreased. Therefore, our results suggest that hSAP contributes to extracellular DNA clearance and the inhibition of plasmid DNA transfection in vivo. This mechanism may be partly responsible for the insufficient immune responses to DNA vaccination in human beings; therefore, it may serve as a novel target for the improvement of DNA vaccines and DNA-based gene therapy.

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Acknowledgements

This work was funded by Key Program (No. 30530660) from National Natural Science Foundation of China, and Basic Research Program (No. 04JC14004) from the Science and Technology Commission of Shanghai.

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  1. Department of Medical Genetics, Second Military Medical University, Shanghai, People's Republic of China

    Y Wang, Y Guo, X Wang, J Huang, J Shang & S Sun

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Correspondence to S Sun.

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Wang, Y., Guo, Y., Wang, X. et al. Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine. Gene Ther 19, 70–77 (2012). https://doi.org/10.1038/gt.2011.67

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