Receptor-Mediated Gene Delivery Employing Adenovirus-Polylysine-DNA Complexes
Gene transfer to eucaryotic cells may be accomplished by capitalizing on endogenous cellular pathways of macromolecular transport. In this regard, gene transfer has been accomplished via the receptor-mediated endocytosis pathway employing molecular conjugate vectors (Wu and Wu, 1987; Wu et al., 1989; Wagner et al., 1990; Wagner et al., 1991b; Cotten et al., 1990; Curiel et al., 1992a; Huckett et al., 1990; Rosenkranz et al., 1992). The molecular conjugate is a synthetic bifunctional agent employed to serve two functions: binding of the heterologous DNA to form a conjugate-DNA complex, and attachment of the conjugate-DNA complex to the target cell to facilitate internalization. The initial step of binding the heterologous DNA to form a conjugate-DNA complex is mediated through a domain of the conjugate comprised by a polycation amine, such as polylysine. This electrostatic interaction between the negatively charged DNA and the positively charged DNA-binding domain serves not only to bind the DNA, but also to condense it into a compact toroid structure (Wagner et al., 1991a). As the ligand is covalently linked to the polylysine DNA-binding domain, after binding of the DNA, at least a portion of the ligand is presented on the surface of the complex, free to interact with its cognate receptor. The attachment of the conjugate-DNA complex to the target cell is then mediated through the specificity of the ligand domain for its corresponding receptor. Thus, after the conjugate-DNA complex accomplishes attachment, it is internalized through the corresponding cellular transport pathway.
KeywordsGene Transfer Gene Delivery Cell Vesicle Ligand Domain Hexon Protein
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