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Retroviral risk

Gene therapy with retroviral vectors can increase the risk of developing leukemia.

Jonathan Weitzman(jonathanweitzman@hotmail.com)

Gene therapy strategies have been riddled with technical problems and much-publicized risks. In the April 19 Science, Zhixiong Li and colleagues deal another blow to gene therapy (Science 2002, 296:497).

They found that when they used replication-defective retroviruses to deliver a marker gene to mouse bone marrow cells, the animals developed leukemia. Li et al. transplanted the bone marrow cells into irradiated recipients; all these animals developed hematopoietic disorders after six months. All the diseased mice had the same leukaemic clone with a single integrated vector copy. The insertion event induced expression of the Evi1 gene, encoding a transcription factor linked to acute myeloid leukemia. The authors suggest that the marker transgene may also contribute to tumor formation.

The risk of cancer is another factor that must be considered in future gene therapy trials.

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