A new twist on genetic immunization has been reported by researchers at the University of Vienna, Austria. Until recently, most genetic vaccines under development have been based on DNA; however, in a recent report (Nat. Med. 4:1438, 1998), Christian Mandl and his colleagues have demonstrated the efficacy of an RNA-based vaccine. They showed that mice inoculated with an RNA vaccine developed from the virus that causes tick borne encephalitis (TBE) survive subsequent infection with wild-type TBE virus. After in vitro synthesis of TBE genomic RNA in Escherichia coli, the RNA was purified, used to coat gold beads, and inoculated into mice using a gene gun. According to the authors, only 0.1 ng of RNA was sufficient for an infectious dose. In contrast, an attenuated form of the virus created by mutations in a noncoding region of the virus was able to confer protection against live virus at a dose of 5 ng of RNA. In the future, vaccine developers will have to grapple with the thorny issue of whether DNA or RNA is the better vaccine candidate: "Using RNA, you eliminate some of the concern for potential DNA integration," says Margaret Liu, vice president of vaccine development at Chiron Corporation (Emeryville, CA), "However, there is a possibility of reversion with RNA vaccines."