RT Journal Article SR Electronic T1 Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization JF Science JO Science FD American Association for the Advancement of Science SP 352 OP 354 DO 10.1126/science.273.5273.352 VO 273 IS 5273 A1 Sato, Yukio A1 Roman, Mark A1 Tighe, Helen A1 Lee, Delphine A1 Corr, Maripat A1 Nguyen, Minh-Duc A1 Silverman, Gregg J. A1 Lotz, Martin A1 Carson, Dennis A. A1 Raz, Eyal YR 1996 UL http://science.sciencemag.org/content/273/5273/352.abstract AB Vaccination with naked DNA elicits cellular and humoral immune responses that have a T helper cell type 1 bias. However, plasmid vectors expressing large amounts of gene product do not necessarily induce immune responses to the encoded antigens. Instead, the immunogenicity of plasmid DNA (pDNA) requires short immunostimulatory DNA sequences (ISS) that contain a CpG dinucleotide in a particular base context. Human monocytes transfected with pDNA or double-stranded oligonucleotides containing the ISS, but not those transfected with ISS-deficient pDNA or oligonucleotides, transcribed large amounts of interferon-α, interferon-β, and interleukin-12. Although ISS are necessary for gene vaccination, they down-regulate gene expression and thus may interfere with gene replacement therapy by inducing proinflammatory cytokines.