Retroviral integration profiles: their determinants and implications for gene therapy

Abstract

Retroviruses have often been used for gene therapy because oftheir capacity for the long-term expression of transgenes via stableintegration into the host genome. However, retroviral integrationcan also result in the transformation of normal cells into cancercells, as demonstrated by the incidence of leukemia in a recentretroviral gene therapy trial in Europe. This unfortunate outcomehas led to the rapid initiation of studies examining variousbiological and pathological aspects of retroviral integration. Thisreview summarizes recent findings from these studies, includingthe global integration patterns of various types of retroviruses,viral and cellular determinants of integration, implications ofintegration for gene therapy and retrovirus-mediated infectiousdiseases, and strategies to shift integration to safe host genomicloci. A more comprehensive and mechanistic understanding ofretroviral integration processes will eventually make it possible togenerate safer retroviral vector platforms in the near future. [BMBreports 2012; 45(4): 207-212]

Keywords

• Host genome
• Integration patterns
• Retroviral vectors
• Safety
• Tumorigenicity