The seventh annual meeting of the American Society of Gene Therapy.

nificantly improved performance in motor skills tests relative to control-treated SCA1 mice. These data provide the first in vivo demonstration of efficacy of RNAi for dominant neurodegenerative disease therapy. The third abstract was authored by Hildegund Ertl, who described her group’s efforts to test a new vaccine platform based on E1-deleted adenoviral vectors derived from chimpanzee serotypes. Vectors were engineered to express HIV-1 Gag, with the aim of inducing Gag-specific CD8+ T cells in mice. As initial attempts to develop an HIV vaccine that induces broadly cross-reactive neutralizing antibodies have failed, Ertl’s approach focused on induction of cell-mediated immune responses. A single administration of the vaccines resulted in CD8+ T cell frequencies that were exceptionally specific for the transgene product. Although the cells initially declined after 2-3 weeks, they resurged at later times, suggesting an internal booster effect due to production of Gag by the transduced cells. Gag transcripts could be detected in lymphatic tissues for over a year after a single administration of the replication-defective adenoviral vectors. Interestingly, transcripts were preferentially expressed by activated, Gagspecific T cells. The results support a vaccine concept based on constructs that achieve persistent transgene product expression and thus maintain high frequencies of specific CD8+ T cells. Other positive work on the HIV vaccine front was presented by Harriet Robinson, this year’s featured speaker at the George Stamatoyannopoulos Lecture, chaired by incoming ASGT president, Katherine High. Robinson reported that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster has controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both components of the vaccine expressed the three major immunodeficiency virus proteins, Gag, Pol, and Env. Control has been at the levels found for successful antiretroviral drug treatment, a level that is associated with many years of disease-free life and undetectable frequencies of transmission. Based on the success of the macaque study, multiprotein DNA and MVA vaccines have been prepared for the three major clades of HIV-1. The clade B DNA vaccine has undergone an initial phase I safety trial in humans through the HIV Vaccine Trials Network and is planned for a more extensive safety and dosing study in early 2005. Results were presented from a number of clinical trials involving a variety of vectors and strategies. Katherine High MEETING REPORT