Macrophages as novel cellular vehicles for gene therapy.
Macrophages accumulate in pathological sites, including tumours, atherosclerotic plaques, arthritic joints and sites of infection. This fact led to the concept of introducing ex vivo genetically modified macrophages into a patient, where they would then 'home' to the sites of disease. For this novel and powerful approach to become a reality, the difficulty of efficiently transfecting macrophages and the tendency of transferred macrophages to locate to non-target sites must be overcome. Great progress has been made in the transfection of macrophages using viral vectors, and in the use of stably transfected CD34(+) precursors of monocytes/macrophages, which could allow the bone marrow of patients with genetic disorders to be permanently enhanced with genetically modified cells. Lack of specificity in macrophage homing to diseased sites is proving to be a problem and will most likely need to be circumvented by the use of means such as disease- or site-specific transcriptional targeting to control expression of the therapeutic transgene.
Burke
Bernard
B
Department of Infection, Immunity and Inflammation, Medical Sciences Building, University of Leicester, Leicester LE1 9HN, UK. bb14@leicester.ac.uk
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection