Design of transfection reagents in RNAi therapeutics by chemoinformatics approach

Abstract

RNAi is a natural biological process involving gene silencing or regulation with siRNA and expected to be applied in the therapeutics of gene disorders. The delivery of siRNA into the cell is demonstrated using cationic lipid. The lipid is called ’Transfection reagents’and the development of new reagents has recently advanced. Some relation exists between the chemical structures of the reagents and their properties, but it is not clear yet quantitatively and the development of new reagents depends on the previous studies. In this study we collected the data of the transfection reagents from literature and constructed statistical models of QSAR models of transfection reagents in order to predict the chemical structures of high efficient reagents in future. The descriptors calculated for chemical structures and experimental parameters were used as explanatory variables, and their rate of gene expression was used as an objective variable. In this study we calculated descriptors for the structures of amines and carbon chains separately and constructed the regression models predicting the rate of gene expression. The value of q2 improved in PLS and SVR models compared with the value of q² calculated with the descriptors for the structures of transfection reagents. The descriptors derived from carbon chains had high correlations with the rate of gene expression compared with the correlations of the descriptors derived from amines.