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Blood stem cells carry targeted genes

Researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have genetically altered human blood stem cells to selectively activate genes in developing immune cells. Results of the research in mice, published in the January 15 issue of Blood, shows it's possible to transfer genes into stem cells and activate the immune system to fight cancer and enhance transplantation.

"Blood stem cells represent an important target for the treatment of a variety of blood and immune disorders, so our ability to engineer them to selectively stimulate immune responses opens up new possibilities for gene therapy," says Linzhao Cheng, Ph.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center and director of the study.

Using a gene known to produce a fluorescent protein, scientists transferred it into human adult and cord blood stem cells and injected the cells into immune-compromised mice. The gene transfer into the stem cells was accomplished via a lentivirus, genetically engineered to be safe, with coded instructions for the gene to turn on in a specific type of cell.

Since blood stem cells differentiate and develop into all blood and immune system cells, all descendants of the stem cells had the fluorescent protein gene. However, the gene turns on only when the stem cell developed into one type of immune cell, called an antigen-presenting cell (APC). APCs play a central role in controlling immune system responses.

"The ability to deliver a gene in a stem cell and then have it expressed in one specific type of cell should provide a new way to achieve targeted gene therapy," says Cheng.

Six mice were transplanted with the fluorescent gene made specific for APCs. After 10 weeks, all produced the fluorescent protein in an average of 56 percent of the transplanted cells, and exclusively in APCs. Five control mice were transplanted with the fluorescent gene made universal for all cells and pr
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Contact: Amy Heaps
heapsam@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
8-Jan-2002


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