Gene Therapy and Research Applications of Intrabodies for Human Infectious Diseases

Abstract

Gene therapy is a new form of molecular medicine that holds tremendous promise for the treatment of human infectious diseases. Perhaps no better example of the broad impact of gene therapy for the treatment of human infectious diseases comes from studies on the human immunodeficiency virus, HIV−1. Gene therapy for the treatment of HIV−1 infection and AIDS has captured the interest of a number of investigators as an attractive addition to conventional pharmacologic therapies because alteration of the host cell could potentially confer permanent suppression of viral replication after infection or even lasting protection against viral infection. Several strategies have been investigated that have different, and sometimes overlapping modes of action. One approach is based on enhancement of the immune response against the virus by using genetically modified cells that express viral gene products to induce antiviral cellular immune responses. Another approach uses an extracellular mode of action by secretion from the transduced cell of a factor directly affecting the HIV−1 life cycle (e.g., sCD4-IgG, antigp120 Fab antibody fragments) or of a factor affecting the host’s defense mechanism (e.g., a cytokine). Intracellular Immunization is a third strategy that is aimed at the stable transfer of genetic elements that inhibit viral replication, so-called “resistance genes” into those cells of a patient that are potential targets for viral infection.1–3