Broad Institute leads push for tools to speed gene therapies

Researchers at the Broad Institute in Cambridge are leading a cooperative, industry-funded effort that could speed discovery of numerous targets for new drugs.

Novartis AG, Eli Lilly and Co., and Bristol-Myers Squibb Co. will each contribute $3.6 million over three years to fund the research consortium, and the results will be freely shared with the scientific community.

The project's results will not by themselves provide cures to diseases. Instead, they are creating a set of tools that biotechnology firms and big drug companies can use to speed their own experiments to discover targets for drugs.

''We're creating a tool kit that lets you test the function of every human gene in your own experiment," said Dr. Eric Lander, director of the Broad Institute and one of the principal investigators of the project. ''That's why it's so important that it be made a public resource. We want a thousand people using this tool kit, and we want them competing to discover their own drugs."

Sigma-Aldrich Co., a manufacturer of laboratory supplies, and an academic consortium sponsored by the Taiwanese government, Academia Sinica-National Science Council, are also funding the project, called the RNAi Consortium.

At the heart of the project is the emerging field of RNA interference. A growing number of firms, including Alnylam Pharmaceuticals Inc. of Cambridge, are using RNAi to develop drugs.

Within a cell, DNA is the genetic blueprint that provides instructions on how to operate. RNA serves as a messenger, delivering those instructions to the parts of the cell that manufacture proteins. In diseased cells, faulty proteins are produced that play a role in the disease.

Traditional drug therapies seek to counteract or neutralize the faulty proteins. Emerging genetic therapies seek to identify the genes that give bad instructions and correct them. RNAi is a third approach, in which scientists seek to create drugs that can destroy the messenger RNA before it delivers its harmful instructions within the cell.

The consortium will look at about 15,000 genes that play important roles within cells, and will create RNAi material that can silence each individual gene by not delivering its instructions. Researchers can then identify the role of those individual genes in specific diseases. With the role of the genes better known, it is hoped drug companies can more effectively develop treatments that target those genes.

''By getting a library of inhibitors for every gene, we could systematically study which genes matter for every living process," said Lander.

Performing experiments with the RNAi inhibitors ''will provide the ability to systematically identify the genes underlying disease process and thereby identify previously unknown targets for drug discovery," said Steven Paul, executive vice president of Eli Lilly's research laboratories.

While the RNAi blockers to conduct such experiments will be shared publicly, any discoveries made with the tools will remain the property of the scientists and companies conducting the research.

The project also includes scientists from Massachusetts General Hospital, Dana-Farber Cancer Institute, the Whitehead Institute for Biomedical Research, the Massachusetts Institute of Technology, Washington University, and Columbia University. The Broad Institute is a collaboration of MIT, Harvard University, and the Whitehead Institute.

Jeffrey Krasner can be reached at krasner@globe.com.