Liposome-Mediated DNA Transfer in Eukaryotic Cells: Gene Uptake and Expression in the Host Cell

Abstract

Liposomes have been used to introduce drugs (Poste and Papahadjopoulos, 1976), enzymes (Gregoriadis and Buckland, 1973), mRNA (Dimitriadis, 1978), viruses (Lonberg-Holm et al., 1976; Wilson et al., 1977), and allosteric effectors (Nicolau and Gersonde, 1979; Gersonde and Nicolau, 1979) in a number of different cells. Recently, chromosomes have been entrapped in liposomes and transferred to cells (Mukherjee et al., 1978) and DNA has been introduced into bacterial cells (Fraley et al., 1979) and into plant cells (Lurquin, 1979). Also the expression of the tetracycline resistance gene (TetR) has been observed in E. coli after liposome-mediated transfer of the plasmid pBR322 to these cells (Fraley et al., 1979). Fraley et al. (1981) have used liposomes to encapsulate with high efficiency DNA isolated from SV40 virus. Infection of a permissive monkey cell line with these DNA-loaded liposomes resulted in the expression of the SV40 DNA encapsulated in liposomes with efficiencies comparable to the calcium phosphate method. Wong et al. (1980) isolated, from E. coli a restriction fragment, 875 bp, which encodes for a β-lactamase activity, and entrapped it in liposomes. Incubation of the DNA-loaded liposomes with avian, murine and human cells resulted in the uptake by the cells of the DNA and the expression of a β-lactamase activity as determined by spectroscopic and microbiological methods. Recently, Schaeffer-Ridder et al. (1981) transformed mouse LMTK cells with the liposome-encapsulated thymidine kinase gene and Nicolau and Rottem (1981) transformed M. capriolum with the pBR322 plasmid encapsulated in liposomes, conferring thus tetracycline resistance to this tetracycline sensitive organism. We will discuss here several aspects of the transformation of eukaryotic cells with liposome encapsulated genetic material.