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12 Naked DNA Gene Transfer in Mammalian Cells

Jon A. Wolff


A common supposition concerning gene transfer into mammalian cells has been that the nucleic acid must be carried within a viral vector or complexed with some type of material within a nonviral vector. However, the DNA basis for genetic transmission, the foundation of molecular genetics and gene therapy, was first demonstrated using naked (pure) DNA. In 1928, Griffith found that nonvirulent pneumococcus became virulent when exposed to dead virulent pneumococcus. Avery, MacLeod, and McCarty purified nucleic acid from the dead virulent pneumococcus and showed that it could transform bacteria. Pure DNA’s ability to transmit virulence suggested that DNA was the hereditary material (Avery et al. 1944).

It is well known how Avery’s discovery eventually led to the elucidation of the double helix and the molecular basis for DNA’s endowment as the hereditary material. Another and less appreciated ramification of Avery’s findings is that purified DNA can be transferred and expressed in foreign environments (Miller 1998). In the late 1980s, I became intrigued by the second implication of Avery’s discovery: that DNA not within a viral vector could potentially be delivered directly into the whole organism.

The first demonstration of the genetic basis for viral gene transmission in mammalian cells was also demonstrated using naked nucleic acids. In the late 1950s and early 1960s, it was demonstrated that naked RNA or DNA purified from viral material was able to cause viral infection when delivered to mammalian cells both in culture and in the whole animal (Herriott 1961). The efficiency of transfer...

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