Nature Biotechnology pp 519 - 525

An international collaboration of scientists has demonstrated the promise of gene therapy for combating hepatitis C infections, which affect about 200 million people worldwide. Currently, the protein alpha interferon is the only approved therapeutic for treating hepatitis C infection and in many cases it shows only limited effectiveness. Reporting in the May issue of Nature Biotechnology, scientists demonstrate that adenoviral gene therapy can lead to significant reductions in levels of hepatitis C virus in mice containing virally infected human liver cells.

As hepatitis C lurks within human liver cells, the authors designed their strategy to specifically induce death in those cells harboring the virus, with the hope that this would prevent production of new infectious virus. To accomplish their goal, they turned to a cellular protein called the BID precursor (BH3-interacting domain death agonist precursor), which triggers the killing of cells only when degraded by enzymes called proteases. Because BID precursor is not normally degraded in healthy cells or cells infected with hepatitis C virus, the researchers engineer into BID precursor a recognition site for a protease found in hepatitis C virus. In this way, they hoped that hepatitis C—infected cells exposed to the modified BID molecules would be specifically targeted and killed.

Sure enough, when the authors used adenoviruses to deliver the gene for the modified BID precursor into human liver cells implanted in mice, they found that BID was cleaved only in those cells infected by the hepatitis C virus and expressing the viral protease. In infected cells, BID went on to cause cell death, effectively halting progression of hepatitis infection. In the majority of cases, BID gene therapy resulted in substantial decreases in the quantity of virus; in mild infections, the clearance of virus was complete. The authors' approach holds promise as a therapeutic option for hepatitis C as well as for other types of viral infections.

Nature Biotechnology pp 513 - 518

Scientists have devised a 'smart' material that actively interacts with cells in the body to promote the growth of new bone. By attaching biological molecules to an otherwise inert polymer, Jeffrey Hubbell and colleagues produced an artificial material that mimics the body's own extracellular matrix. The approach, described in the May issue of Nature Biotechnology, was tested in rats and may eventually be useful for healing injured bone or other tissues in human patients.

In one strategy for repairing damaged bone, tissue engineers are developing implants made of a scaffold material and specific proteins (such as BMPs) that coax cells to form new bone. Researchers have tried using extracellular matrix isolated from animals as the scaffold material, but these substances carry a risk of disease transmission and may provoke an immune reaction. Alternatively, researchers have used artificial scaffold materials, but these perform less well because they are passive carriers that do not interact with cells.

Hubbell and colleagues attached two different short protein sequences to an artificial scaffold. One sequence helps cells in the body adhere to the scaffold. The other sequence, which can be snipped in two by cellular enzymes, allows incoming cells to degrade the scaffold and enter new regions of the implant. The degradation of the scaffold in turn releases BMP proteins, stimulating more bone formation. The new scaffold material represents an advance in tissue engineering because it combines several advantages of both natural and artificial scaffolds.