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‘Gene marking’ efforts preceded the use of retroviral derived vectors in gene therapy as delivery vehicles of therapeutic genes. Unfortunately their use in gene therapy is not without serious drawbacks. Indeed, even if retroviral vectors are depleted of most of their genes in order to prevent dangerous infections, insertional mutagenesis can disrupt important genes, such as those involved in the control of cell growth and division, leading to cancer onset. Additionally, introduced viral promoters and enhancer can activate transcription of proto-oncogenes [64 更多：https://www.bmcx.com/ ,65]. For these reasons, analysis of integration sites in the host genomes has to be considered as an essential step in gene therapy protocols. Emblematic was the case of patients with a form of severe combined immunodeficiency caused by a defect in a gene of the X chromosome, who first received a retrovirus derived vector engineered with the correct human gene [66]. Unfortunately, after 3 years, two patients developed a leukemia-like condition owing to the insertion of the retroviral vector in proximity to the LMO-2 (LIM domain only 2) proto-oncogene, as demonstrated by LAM-PCR GW analysis [66].