Retroviral vectors, gene therapy products

The lentiviral vectors have safety concerns similar to the retroviral vector-based gene therapy products (1) the production of a replication competent lentivirus (RCL) during manufacturing and (2) the potential for insertional mutagenesis, resulting in oncogene activation. One concern unique to the lentiviral vectors is the possibility that the vector can be mobilized in vivo,... 

Kotani, H. et al.. Improved methods of retroviral vector transduction and production for gene therapy. Hum. Gene Ther., 5,19,1994. 

Fig. 6.5. Use of helper cell lines in the production of replication-deficient retroviral vectors for gene therapy.

Cumulative experience from 106 monkey-years and 23 human-years of retroviral gene therapy had revealed no side-effects or malignancies. Recently, however, three monkeys used in clinical trials developed T cell lymphomas which were traced to a helper virus-contaminated retroviral vector preparation (Anderson, 1992a). Contamination of defective viral vector stocks by infectious viruses produced in helper cells was a serious problem with the early version of the helper cells. New helper cell lines which greatly reduce the probability of virus production have been developed (Miller, 1990). Eurther, it is also imperative to test the lots of vector virus preparations used in therapy for the presence of other infectious viruses. The probability... 

Sinn P L, Sauter S L, McCray Jr P B (2005). Gene therapy progress and prospects Development of improved lentiviral and retroviral vectors—design, biosafety, and production. Gene Ther. 12 1089-1098. 

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