The utility of adenoviral vectors for gene therapy is currently limited due, in part, to the widespread distribution of the cellular receptor for the adenovirus fiber that precludes the targeting of specific cell types. In order to develop a targeted adenovirus, it is therefore necessary both to ablate endogenous viral tropism and to introduce novel tropism. We hypothesized that these two goals could be achieved by employing a neutralizing anti-fiber antibody, or antibody fragment, chemically conjugated to a cell-specific ligand. To test this concept, we chose to target the folate receptor, which is overexpressed on the surface of a variety of malignant cells. Therefore, we conjugated folate to the neutralizing Fab fragment of an anti-fiber monoclonal antibody. This Fab-folate conjugate was complexed with an adenoviral vector carrying the luciferase reporter gene and was shown to redirect adenoviral infection of target cells via the folate receptor at a high efficiency. Furthermore, when complexed with an adenoviral vector carrying the gene for herpes simplex virus thymidine kinase, the Fab-folate conjugate mediated the specific killing of cells that overexpress the folate receptor. This work thus represents the first demonstration of the retargeting of a recombinant adenoviral vector via a non-adenoviral cellular receptor.

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Interracial unions and same-sex unions were rare and secretive in the past because U.S. society was organized to suppress such unions. The rise of same-sex and interracial unions in the past few decades suggests changes in the basic structure of U.S. society. Young adults have been marrying later, and single young adults are much less likely to live with their parents. The independence of young adults has reduced parental control over their children's choice of mate. Using microdata from the U.S. Census, this article shows that interracial couples and same-sex couples are more geographically mobile and more urban than same-race married couples. The authors view the geographic mobility of young couples as a proxy for their independence from communities of origin. The results show that nontraditional couples are more geographically mobile even after individual and community attributes are taken into account. Same-sex couples are more likely to be interracial than heterosexual couples, indicating that same-sex and interracial couples are part of a common fabric of family diversification. The article discusses related historical examples and trends.