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Please quote Nature Biotechnology as the source of these items.

The July 2003 issue of Nature Biotechnology is available online.

 July 2003 Previous | Next

Virus therapy attacks cancer cells

Nature Biotechnology pp 771 - 777

Researchers have come up with an ingenious means of engineering a virus so that it selectively replicates in and destroys tumor cells. Because the virus is unable to attack normal cells, it may prove useful as a supplement to traditional cancer treatments, which do not discriminate between normal and tumor cells and often cause debilitating side effects. The new type of adenoviruses, described by Richard Vile and coworkers in the July issue of Nature Biotechnology, replicates in cells with cancer-associated genetic mutations.

Vile and his team engineered into their virus a special type of mRNA ‘stability’ sequence that causes a gene (E1A) essential for viral replication to be degraded in normal cells, thus inhibiting reproduction of the virus. Because mRNA stability is improved in the presence of a protein called RAS—which is less abundant in normal cells, but common in certain cancer cells—the researchers hypothesized that their virus would, however, selectively replicate in and destroy tumor cells. Sure enough, when they injected the virus into tumors implanted in mice, it replicated and reduced tumor growth. The approach provides a step towards generating truly selective viral therapies against cancer.


A conditionally replicating adenovirus targeted to tumor cells through activated RAS/P-MAPK-selective mRNA stabilization pp 771 - 777
Atique Ahmed, Jill Thompson, Lisa Emiliusen, Stephen Murphy, R Daniel Beauchamp, Kaori Suzuki, Ramon Alemany, Kevin Harrington & Richard G Vile
Published online: 8 June 2003 | doi:10.1038/nbt835
Abstract | Full text | PDF
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Safeguard for GM therapy

Nature Biotechnology pp 785 - 789

Scientists in Belgium have come up with a way of preventing live bacteria used in an experimental biotechnology therapy from propagating and disseminating in the environment. A modified form of a dairy bacterium Lactococcus lactis that normally lives in the gut is soon to be tested clinically to see if it can treat inflammatory bowel disease—rather like eating live yogurt to cure an upset tummy. Because the bacterium is genetically modified, however, it must be prevented from surviving outside the patients’ bodies. In the July issue of Nature Biotechnology, Lothar Steidler and colleagues describe a genetic modification strategy (GM) for doing just that. By substituting an essential survival gene in the bacterium with the therapeutic gene (interleukin-10), they engineer an organism that delivers IL-10 to fight inflammatory bowel disease, but is hampered from persisting outside of the body.

The researchers' strategy was to substitute a gene producing the nutrient thymidine (which is essential for surviving in the environment but not necessary for survival in the intestine because thymidine is more abundant) with the therapeutic gene encoding interleukin-10. The therapeutic approach has prompted the Dutch government to approve the use of the bacteria to treat inflammatory bowel disease in human trials—the first application of a genetically modified bacterium in human therapy.


Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10 pp 785 - 789
Lothar Steidler, Sabine Neirynck, Nathalie Huyghebaert, Veerle Snoeck, An Vermeire, Bruno Goddeeris, Eric Cox, Jean Paul Remon & Erik Remaut
Published online: 15 June 2003 | doi:10.1038/nbt840
Abstract | Full text | PDF
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Stem cells cure diabetes-like disease in mice

Nature Biotechnology pp 763 - 770

Bone marrow stem cells transplanted into mice with a diabetes-like illness raise the animals’ insulin to near-normal levels and significantly reduce their blood sugar levels, according to a report in the July issue of Nature Biotechnology. Mickie Bhatia and colleagues found that the transplanted stem cells did not produce insulin themselves but stimulated regeneration of the animals’ own pancreatic cells.

While the approach shows promise, it has not yet been studied in humans, and further research will be needed before it can be considered as a therapy for people with diabetes.


Bone marrow–derived stem cells initiate pancreatic regeneration pp 763 - 770
David Hess, Li Li, Matthew Martin, Seiji Sakano, David Hill, Brenda Strutt, Sandra Thyssen, Douglas A Gray & Mickie Bhatia
Published online: 22 June 2003 | doi:10.1038/nbt841
Abstract | Full text | PDF
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ISSN: 1087-0156
EISSN: 1546-1696
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