Receptor-Mediated Targeted Gene Delivery Using Asialoglycoprotein-Polylysine Conjugates

Abstract

Delivery of exogenous DNA into cells has been in the forefront of genetic research, both in basic and clinical sciences. Many techniques have been developed to introduce foreign genes into mammalian cells in vitro (Gopal, 1985; Harland and Weintraub, 1985; Potter et al, 1984; Williams et al., 1984; Nicolau and Sene, 1982; Zhou et al., 1991; Graham and Van der Eb, 1973). For example, one of the oldest and most popular methods involves a co-precipitation of DNA with calcium phosphate. These insoluble particles are internalized within the host cells (Loyter et al., 1982). A portion of the DNA containing a gene of interest can be expressed in vitro. Indeed, calcium phosphate precipitates have also been used successfully in vivo by direct injection into organs resulting in transfection of cells in animals and subsequent expression (Dubensky et al., 1984a; Benvenisty and Reshef, 1986a). For example, Benvenisty and Reshef detected expression of chloramphenicol acetyltransferase (CAT), in mainly liver and spleen, after intraperitoneal injection of calcium phosphate precipitated plasmids which contained CAT marker gene (Benvenisty and Reshef, 1986b). Similarly, Dubensky and associates were able to demonstrate viral replication and acute infection after polyoma viral DNA was directly introduced into the liver or spleens of mice (Dubensky et al., 1984b).