Pharmacodynamic approach to study the gene transfer process employing non-viral vectors

In the present work we set out to apply pharmacodynamic concepts derived fr om dose-response curves (Potency and Efficacy) to characterize the gene tra nsfer efficiency of a vector:DNA complex. We employed two widely used vecto rs, the cationic lipid DOTAP (N,N,N-trimethyl 1-2-3-bis (1-oxo-9-octadeceny l)oxy (Z,Z)-1-propanaminium methyl sulfate) and the cationic polymer PEI (p olyethylenimine, 800 kDa) to transfect several constructions of the green f luorescent protein cDNA. The analysis of dose-response curves indicated tha t in all cases the goodness-of-fit was > 0.99. Potency is a measure that pr ovides information on gene activity per amount of DNA. Efficacy is a measur e of maximum gene expression achievable using a specific vector:DNA complex , and depends on both the intrinsic efficacy of the gene (evaluated using d ifferent vectors to transfer the same gene construct) and on vector efficac y in DNA delivery (evaluated using a single vector to deliver different gen e constructs). The results suggest that Potency and Efficacy are objective parameters for describing and comparing the goodness of vectors, as well as the intrinsic efficacy of a given gene construct. Furthermore, they are us eful tools that may contribute to a better understanding of the mechanistic gene transfer process of each vector. BIOCHEM PHARMACOL 60;12:1845-1853, 2 000. (C) 2000 Elsevier Science Inc.