In an approach that could significantly increase the efficiency of a variety of gene therapies, researchers at the University of Washington (Seattle, WA) have demonstrated that the addition of a chromatin insulator can protect a retroviral gene vector from position effects that otherwise tend to silence inserted genes. Although they are used widely in gene therapy, murine retrovirus-based vectors integrate randomly and frequently insert themselves into the transcriptionally silent heterochromatin that makes up the bulk of a cell's genome.

In the new work, described in the 1 August issue of PNAS (97, 9150–9155, 2000), the researchers flanked a reporter gene in a retroviral vector with the HS4 chromatin insulator from the chicken β-globin locus control region. Chromatin insulators, which shield promoters from the activity of nearby regulatory elements, have been found in a variety of species. In cultured cells and mice transplanted with transduced bone marrow, the flanked vector was expressed in a significantly higher fraction of transduced cells than a control lacking the insulators. David Emery, a researcher at the University of Washington and first author on the paper, cautions that “it is possible this and other chromatin insulators may not work with every promoter and in every tissue,” but adds that the team is now testing a variety of constructs for possible clinical use.