Complement Activation by Polylysine-DNA Complexes

Abstract

Polylysine-DNA complexes represent one major class of vectors currently used in gene transfer in cell culture. A number of receptor ligands have been coupled to polylysine (for reviews see Wu, et al, 1993; Cotten et al, 1993; Perales et al, 1994). DNA complexed with such conjugates can be specifically targeted to cells displaying the desired receptor, taken up via receptor-mediated endocytosis and if the DNA escapes intracellular degradation it can be expressed. Vectors of this design work highly efficiently if an endosomedisrupting moiety is included in the DNA complex (Curiel et al, 1991; Plank et al, 1994). The targetability of such vectors should make them particularly appropriate for intravenous application. Successful gene transfer via the intravenous route has been reported (Wu and Wu, 1993 (review); Ferkol et al, 1993; Perales et al, 1994; Stankovics et al, 1994; Ferkol et al, 1995). However, as with other synthetic gene transfer vectors (Zhu et al, 1993) reproducibility represents a major problem when it comes to intravenous application. This in part may be due to parameters affecting the stability of such DNA complexes in blood and their interaction with blood components. Such interactions may limit the half-life and targetability and result in rapid clearance by the reticulo-endothelial system (RES).