ABSTRACT

To be expressed in target cells for gene therapy, DNA should be delivered to the nucleus through physiological and cellular barriers such as the cell membrane, endosomal membrane, and nucleus membrane.1,2 Therefore, an efficient carrier should have the following characteristics. First, the carrier should condense the DNA into a small size and mask the negative charge of DNA for

efficient internalization. Second, the carrier should have a specific ligand for targeting DNA to a specific tissue. Third, the carrier-DNA complex should escape the endosome to avoid lysosomal degradation. Fourth, the DNA should be transferred into the nucleus for transcription. Poly(Llysine) (PLL) has been widely used for gene delivery because of its excellent characteristics as a gene carrier. PLL has positive charges at its ε-amines, which contribute to the condensation of negatively charged DNA. PLL can protect DNA from nucleases, which is an essential characteristic for in vivo gene delivery. In addition, a targeting moiety can be easily coupled to PLL by chemical conjugation for targeting delivery.