Nature Biotechnology pp 639 - 644

Scientists have developed a strategy for treating hepatitis B infection, which affects several hundred million people worldwide and can lead to chronic liver diseases such as cirrhosis and cancer. Although hepatitis B can be effectively prevented through immunization, once an individual is infected with the virus, currently available therapeutics are of only limited effectiveness. Reporting in the June issue of Nature Biotechnology, a group of scientists led by Mark Kay at the Stanford University School of Medicine show that progression of the hepatitis B virus in mice can be effectively contained by inactivating virus-specific RNA in the liver using a tiny piece of ribonucleic acid.

The research is the first time small interfering ribonucleic acid molecules (siRNAs) have been used to curb a viral infection in an animal. By injecting an siRNA that targets hepatitis virus into the tails of mice, the researchers were able to disrupt hepatitis B virus replication and proliferation. The siRNA molecules were designed to specifically bind to two hepatitis B virus RNAs in the liver cells and, following a complex chain of events, ultimately interfere with hepatitis B virus replication. The approach resulted in an 84.5% reduction in hepatitis B virus surface antigen (HBsAg) and a >99% reduction in the hepatitis B virus core antigen (HBcAg). The approach holds promise as a therapeutic option not only for hepatitis B but also for other types of viral infections.

Nature Biotechnology pp 645 - 651

A paper by Zan et al. in the June issue of Nature Biotechnology describes the first ever "knockout" lab rats, allowing researchers to study the effect of specific gene defects on rat physiology.

Mice in which the function of genes has been ‘knocked out’ by mutagenesis have proven indispensable for understanding the impact of gene function on physiology. Typically, mouse knockouts are made from genetically altered embryonic stem cells. But as scientists have not been able to isolate embryonic stem cells from rats, Zan et al. took a different approach. By designing a test that rapidly identifies rare rats that contain a mutation in a gene of interest induced by a chemical, Zan et al. succeeded in producing rats carrying knockouts of two genes associated with breast cancer, Brca1 and Brca2.

The achievement is particularly significant because of the lab rat’s importance as a model of many other human diseases, including diabetes, hypertension, and neurological disorders. The ability to make knockout rats will aid scientists working to unravel the genetic roots of these disorders.