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Has the viral vector element WRE been modified such that the oncogenic protein has been replaced or has a modified OPRE?

Our WPRE sequence is wild type. There is an "optimized" version in which start codons have been mutated and the X protein promoter removed. Liver tumors have arisen from mice injected with lentivirus expressing Factor IX and there is some speculation that it arose because of the truncated X protein encoded within the WPRE sequence. However, it is not clear whether truncated forms of WPRE are safer than wild type. We recommend that biosafety level 2 (BSL2) be used for work with our lentiviral vectors.