Cancer Risk in Gene Therapy Higher than Thought

In a discovery that may lead to safer gene therapy techniques, a study has found that the genetically engineered mouse virus used in gene therapy trials tends to insert itself at the beginning of a gene in the target cell, potentially disrupting the gene's normal function and contributing to effects such as cancer. The findings were reported in the June 13, 2003, issue of Science.

In current gene therapy, doctors insert functional copies of a gene into target cells of the body to cure genetic illnesses. Different types of viruses have been genetically engineered so they can infect target cells and integrate their genes into the chromosomes of those cells. One of the most widely used viruses is the Moloney murine leukemia virus (MoMuLV), a mouse retrovirus that can also infect human cells. In January 2003, two children being treated by French researchers for an immunodeficiency disease developed a leukemia-like condition. Doctors now believe the children developed leukemia because the MoMuLV inserted therapeutic genes next to a gene known to promote blood cancer.

Previously, MoMuLV was thought to randomly integrate into the genome of target cells, but scientists lacked the means to study the process in a large-scale manner. Now, a laboratory technique that allows researchers to rapidly sort through the entire genome of hundreds of individual cells to see where the retroviruses have inserted themselves has been developed by a team from the National Human Genome Research Institute (NHGRI; Bethesda, MD, USA) and the US National Cancer Institute (NCI).

"MoMuLV does not insert its genes randomly, as had been previously thought,” said senior author Dr. Shawn Burgess, of the Genome Technology Branch of NHGRI. "It likes to land right at the beginning of a gene, potentially affecting the way the gene works. The virus is eight times more likely than random to land at the beginning of a gene. We don't know why it has this specificity.” Dr. Burgess also noted that MoMuLV seems to have a clear preference for more actively expressed genes.




Related Links:
Human Genome Research Institute
National Cancer Institute