[Molecular conformation and expression efficiency in the hepatocyte targeting gene drug]

To modulate the molecular conformation of the hepatocyte targeting drug to increase exogenous gene expression efficiency in the targeted cell.

Some specific auxiliary molecules were added to the gene drug its molecular liquid conformation was investigated under the electron-microscope and they were transfected into human hepatoma cell line BEL-7402 in vitro. We detected IFN-gamma gene expression product by ELISA and screened out the most efficient drug molecules.

Due to various concentrations of auxiliary molecules, the conformation of hepatocyte targeting drug changed, including floccule, globulous, stringbeads, bacillform and chromosome-like mixture. While the most efficient expression conformation was the bacilliform and chromosome-like mixture and didn't need to inhibit the lysozyme activity, the expression efficiency of such drug molecules was much higher than that of the liposome targeting vector.

The molecular drug conformation had much influence on targeted gene expression efficiency in gene therapy. Bacilliform and chromosome-like mixture may be the most efficient expression conformation to construct drug molecules in ASOR targeted hepatocyte gene therapy. So we put forward a new concept "chromosome mimic conformation" in screening out the most efficient molecular drug conformation in gene therapy.