Genetica, Inc. Develops High Throughput RNAi Tool for Drug Target Validation.

Business Editors and Health/Medical Writers

CAMBRIDGE, Mass.--(BW HealthWire)--Jan. 29, 2002

The biotechnology company Genetica, Inc has developed a powerful, high throughput tool for target validation in the drug discovery process based on research carried out by scientists at Cold Spring Harbor Laboratory. The research, published today in the Proceedings of the National Academy of Sciences (PNAS), demonstrates stable suppression of gene expression in mammalian cells using the RNA interference (RNAi) pathway. The research significantly advances the understanding of this recently discovered pathway and expands its use in elucidating mammalian gene function.

"The ability to efficiently determine the role of specific genes and gene products has become one of the most pressing challenges in drug discovery," says David Beach, Ph.D., President of Genetica, Inc. "This research and other research in our laboratories has allowed Genetica to develop a cost-effective, high throughput platform for drug target identification and validation using RNAi. Also, owing to RNAi's effectiveness in the embryonic cells of mice, which closely resemble human cells, there are potential applications of this technology in creating mice with specific gene 'knock-downs,' enabling the examination of phenotypes that develop over long time periods."

Dr. Beach added that RNAi is one of several approaches Genetica has developed to accelerate drug discovery. In addition to RNAi, the Company has advanced a number of novel cellular genetic tools to overexpress desired genes in a wide range of human and other cell types. Genetica has particularly applied one of these technologies, a retroviral tool called CELLx, to antibody production.

Gregory Hannon, Associate Professor at Cold Spring Harbor Laboratory, principal investigator in the new study, and a founder of Genetica says, "RNAi has emerged as a highly promising research tool for determining gene function. Our research demonstrates that RNAi can lead to stable silencing of gene expression in mammalian cells, and thus generate lasting `loss of function' phenotypes.

"Up to now, eliciting stable suppression of gene expression has been limited to plants and some model systems such as worms (C. elegans) and fruit flies (Drosophila). Now, we can apply RNAi to mammalian cells to rapidly assess gene function." Copies of the article titled, "Stable Suppression of Gene Expression by RNAi in Mammalian Cells," are available from the PNAS news office (tel. [phone], email [e-mail]). The study was carried out by Hannon and his Cold Spring Harbor Laboratory colleagues Patrick J. Paddison and Amy A. Caudy.

First discovered in 1995, RNAi, a form of post-transcriptional gene silencing, is a natural process that involves inactivating genes via double-stranded RNA (dsRNA). Once inside cells, the dsRNA is cut by a specific enzyme and then rendered single stranded. Next, the resulting single-stranded RNA fragments bind to the RNAi-induced silencing complex (RISC), which then seeks out and destroys the messenger RNA (mRNA) that is complementary to the RNA fragments from the dsRNA. By destroying the mRNA, the activity of a specific gene is silenced.

Hannon and his colleagues at Cold Spring Harbor Laboratory had previously identified the enzyme responsible for the processing of dsRNA and initiation of the RNAi pathway, in studies published in the January 18, 2001 issue of Nature. In the August 9, 2001 issue of Science, Hannon's group described the discovery of another key protein involved in RNAi. In the new study -- which was supported by Genetica as well as the National Institutes of Health -- the scientists employed methods similar to those used in Drosophila to trigger gene silencing in mouse cells. The researchers demonstrated suppression of gene expression using long dsRNA of approximately 500 base pairs in length. Previous research showed only transient suppression in mice using small RNAs of about 22 base pairs in length. In addition, the new study demonstrates the ability of RNAi to establish silencing in different mouse cell types including embryonic stem cells, embryonal carcinoma cell lines, and some somatic cells.

Genetica is a privately held biotechnology company focused on cellular genetics, in particular the use of a novel set of genetic tools both to enhance the pace of drug discovery and to genetically manipulate cultured cells and whole organisms. Genetica's unique approach may be used to determine disease pathways in human cells, validate targets for small molecule drug discovery, and discover novel biopharmaceuticals and diagnostics.