Insertional Mutagenesis from a Viral Vector

Integrated viral sequences can dysregulate genes.

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© 2003 AAAS

RNA Fluorescence In Situ Hybridization reveals transcription at the LMO2 promoter for patients P4 (a) and P5 (b). In each case, an antisense LMO2 probe and an antisense c probe were hybridized to T cells recovered from the patients. (From S. Hacein-Bey-Abina et al., Science, 302:415–9, 2003.)

Integrated viral sequences can dysregulate genes. Thus, the specter of insertional oncogenesis had loomed in the background of every gene therapy trial that used an integrating viral vector. "The original calculations were that the risk would be very small because the genome is big," says Jennifer Puck, a gene therapist at the National Human Genome Research Institute (NHGRI). "No one recognized any reason why retroviruses should be more often inserted into any one place than any other."

Yet the first two of this issue's Hot Papers, from Frederic Bushman's lab at the Salk Institute in La Jolla, Calif.,1 and Shawn ...

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