Visualization of the Intracellular Defense Mechanism Against Exogenous Genes

・Use of single-molecular fluorescence imaging technology to elucidate the fate of DNA introduced into a living cell.

・Discovery that the defense mechanism against exogenous gene expression, and DNA degradation activity, differ across cell lines.

・New insights that contribute to the elucidation of the molecular basis for DNA medicines and gene therapy, and to making them more efficient.

Overview

We have developed a technology for visualizing the behavior of DNA molecules within living cells, and elucidated the intracellular fate of DNA introduced from the outside. This research makes use of single-molecular fluorescence imaging technology to visualize and analyze the behavior of exogenous DNA that were introduced into the cell from outside. We found that degradation of DNA in the cytoplasm serves as one important defense mechanism against exogenous gene expression, and blocks the effective expression of exogenous genes. We also discovered that this nuclease activity varies greatly depending on the cell type.Until now, the fate of exogenous DNA introduced into a cell was treated as a black box. The present research provides a theoretical backbone for gene introduction research previously conducted by trial-and-error, and is expected to contribute to the elucidation of the molecular basis of DNA medicines and gene therapy, and to make them more efficient.

This research was jointly conducted between the Bioanalytical Research Group of the Biomedical Research Institute (Research Director Yoshihiro Ohmiya) of the National Institute of Advanced Industrial Science and Technology (AIST) (President Ryoji Chubachi), and by the Nano-Bio Probe Research Team (Team Leader Takashi Jin) of the RIKEN Quantitative Biology Center of RIKEN (President Hiroshi Matsumoto).