Gene therapy with histones

In the October 10 Proceedings of the National Academy of Sciences, Balicki et al. report that histone H2A can be used to increase the efficacy of gene therapy (Proc Natl Acad Sci USA 2000, 97:11500-11504). Histone H2A has been used in the past to coat DNA prior to transfection. It appears to work both because of its positive charge and some other property, which is presumed to be its nuclear-localizing activity. Balicki et al. use H2A for in vitro delivery of the gene for interleukin-2 (IL-2) to murine neuroblastoma cells. IL-2 can increase the immunogenicity of tumor cells so that the host immune system attacks not only the re-introduced cells, but distant tumor masses. Histone H2A outperforms a commercially available transfectant called Superfect by inducing larger amounts of murine interferon release, and causing rejection of primary tumors rather than a partial reduction in tumor growth.