Replacing retroviruses

NIH advisory committee plans to explore alternative vectors for gene therapy | By Hannah Kamenetsky

The National Institutes of Health Recombinant DNA Advisory Committee (RAC) will consider a wide-ranging set of issues over the next year, including what gene therapy vectors could replace retroviruses and what is required to win FDA approval of new vectors so they can be used in clinical trials, members said at a June 18 meeting in Bethesda, Maryland.

"We were looking in the broadest sense at the state of the art of retroviral vectors," said committee member Madison Powers, director of the Kennedy Institute of Ethics at Georgetown University, in explaining the group's choice of topics for future discussion. Another question that arises, Powers said, is what safety modifications could be adopted for use of retroviral vectors in clinical settings.

Although Powers didn't make the direct link in his comments, clinical trials using retroviruses have attracted closer scrutiny since last fall, after patients in French studies using retroviruses to insert new genes in blood stem cells to treat X-linked severe combined immunodeficiency syndrome (X-SCID) were found to have developed leukemia.

In February 2003, RAC recommended that retroviral gene transfer for X-SCID be limited to patients for whom stem cell therapies had failed or for whom stem cell donors couldn't be found. The committee did not go so far as to recommend halting clinical trials using retroviruses to treat other diseases, including non–X-linked SCID.

Looking ahead, Powers said, one large question is whether other vector types would be appropriate substitutes for retroviruses, and if so, what is needed to develop these new vectors in terms of clinical use, animal models, and Food and Drug Administration approval. "I'd like to know what it takes from the beginning to get a vector approved for use," said Maxine Linial of the Fred Hutchinson Cancer Research Center.

Another issue of interest is whether there are ways to make RAC's interaction with institutional biosafety committees, institutional review boards, and international oversight committees "more fluid and more useful," Powers said.

Further topics that committee members want to put on their agenda include: risk–benefit analyses of using retroviruses in clinical trials and whether there are types of studies for which these vectors shouldn't be used, haploidentical bone marrow transfer studies, large animal models, and statistical methodology used in phase I clinical trials. The committee is scheduled to meet again September 17–19, 2003.