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Florigene, CSIRO, Galapagos Genomics, Dowpharma, Nastech, ASBMB, Rosetta Genomics


Florigene Uses CSIRO RNAi Technology to Make Blue Rose

Australia's Commonwealth Scientific and Industrial Research Organization announced this week that its RNAi technology has been used to create the world's first blue rose.

Florigene, an Australia-based company that is part of the Japanese Suntory company, used CSIRO's technology to silence in roses the dihydroflavonol reductase gene, which makes a protein key to the production of pigments in the flower.

According to CSIRO, researchers at Florigene inserted into the roses a gene from pansies, called delphinidin, to "open the door to the production of blue pigment in the rose flowers." Then, they replaced the rose DFR gene with a DFR gene from irises that causes the production of blue pigments.

"Subsequently, a rose with a blue flower was produced," said CSIRO.

CSIRO noted that it is expected to be about three years before blue roses are commercially available.

Galapagos Inks Drug Target Characterization Deal with TNO

Galapagos Genomics said this week that it has entered into a collaboration with TNO, a Dutch applied science research organization, to characterize potential drug targets provided by Galapagos.

According to the companies, the project is part of a research program sponsored by the Dutch government, and will combine the capabilities of each partner to develop protein technologies that will allow progression of the disease targets to the drug-discovery stage. The collaboration will entail the development of expression systems, protein purification, and protein activity methodologies.

Galapagos, which began offering target-discovery services since it was founded in 1999, has been transforming itself into a small-molecule drug-discovery company. In a step toward this goal, the company recently split off its viral-based discovery and validation operations into a stand-alone unit called Galadeno (see RNAi News, 9/24/2004).

Dowpharma to Manufacture siRNAs for Alnylam Drug Programs

Alnylam Pharmaceuticals announced this week that it has signed on Dowpharma, a business unit of The Dow Chemical Company, to manufacture and supply RNAi drug candidates for its therapeutic-development programs.

Under the contract service agreement, Dowpharma will provide Alnylam with large quantities of GMP-certified siRNAs necessary for near-term toxicology and clinical studies of RNAi therapeutic candidates. Alnylam noted that the siRNAs provided by Dowpharma would be used in "certain Alnylam programs," including those in age-related macular degeneration and respiratory syncytial virus.

Additional terms of the arrangement were not disclosed.

Nastech to Present Therapeutic RNAi Data at ASBMB Meeting

Nastech said this week that it would be presenting preclinical data from its therapeutic RNAi program in rheumatoid arthritis at the 2005 American Society for Biochemistry and Molecular Biology annual meeting.

The event is being held April 2-6 in San Diego. The RNAi data is slated for presentation on April 5.

While Nastech specializes in intranasal drug delivery, the company reported about a year ago that it took a license to the Carnegie Institute's Fire-Mello patent, and that it would be exploring the use of RNAi in conjunction with its delivery technologies for therapeutic applications (see RNAi News, 2/6/2004).

Rosetta Genomics Closes $4 Million Private Equity Round

MicroRNA technology start-up Rosetta Genomics has closed a $4-million financing round recently, according to a news report.

Rosetta has developed a way to discover microRNA genes, and hopes to begin generating revenue in 2006, according to Globes Online. The current financing round will help the company expand its IP estate and pay for clinical trials on animals for the miniature molecules it has developed.

The round, Rosetta's third, was led by Kadima High Tech. Other investors included Israeli drug maker Teva Pharmaceuticals; Leon Recanati; GlenRock Israel; VCON Chairman and CEO Yair Shamir; Agis chairman Moshe Arkin; Uzia Galil; Yoav Chelouche of the Fantine Group; Nathan Hod, former CEO of DSP Communications; Mordechai Segal, cofounder of Libit Signal Processing; Ami Lidor of Lidor Chemicals; Moshe Many, former president of Tel Aviv University, and chairman of Teva's R&D committee; Michael Sela, Israel Prize laureate and former president of the Weizmann Institute of Science; First International Bank of Israel Chairman Joshua Rosensweig; Ehud Arad of the law firm Bach, Arad, Scharf, & Co.; and investor Michael Davis.

Structural Insights into RNAi Mechanism Published

Two letters published in the March 31 issue of Nature report on structural features important for the silencing of target genes by an RNA-induced silencing complex.

In one letter, David Barford and colleagues at the Institute of Cancer Research in London reported the crystal structure of a Piwi protein from Archaeoglobus fulgidus "in complex with an siRNA-like duplex, which mimics the 5' end of a guide RNA strand bound to an overhanging target messenger RNA.

"The structure contains a highly conserved metal-binding site that anchors the 5' nucleotide of the guide RNA," the researchers wrote in their letter. "The first base pair of the duplex is unwound, separating the 5' nucleotide of the guide from the complementary nucleotide on the target strand, which exits with the 3' overhang through a short channel. The remaining base-paired nucleotides assume an A-form helix, accommodated within a channel in the PIWI domain, which can be extended to place the scissile phosphate of the target strand adjacent to the putative slice catalytic site."

The researchers noted that "this study provides insights into mechanisms of target mRNA recognition and cleavage by an Argonaute-siRNA guide complex."

In the second letter, Dinshaw Patel and colleagues from Memorial Sloan-Kettering Cancer Center and Rockefeller University detail the crystal structure of A. fulgidus Piwi protein bound to dsRNA.

According to the researchers' letter, "the PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC. … We report the crystal structure of Archaeoglobus fulgidus Piwi protein bound to double-stranded RNA, thereby identifying the binding pocket for guide-strand 5'-end recognition and providing insight into guide-strand-mediated messenger RNA target recognition."

According to the letter's authors, "the phosphorylated 5' end of the guide RNA is anchored within a highly conserved basic pocket, supplemented by the carboxy-terminal carboxylate and a bound divalent cation. The first nucleotide from the 5' end of the guide RNA is unpaired and stacks over a conserved tyrosine residue, whereas successive nucleotides form a four-base-pair RNA duplex," the stated. "Mutation of the corresponding amino acids that contact the 5' phosphate in human Ago2 resulted in attenuated mRNA cleavage activity. Our structure of the Piwi-RNA complex, and that determined elsewhere, provide direct support for the 5' region of the guide RNA serving as a nucleation site for pairing with target mRNA and for a fixed distance separating the RISC-mediated mRNA cleavage site from the anchored 5' end of the guide RNA."

Finally, in an article published in the April issue of Nature Structural & Molecular Biology, Leemore Joshua-Tor and colleagues from Cold Spring Harbor Laboratory report that recombinant human Argonatue2 can combine with an siRNA to form minimal RISC that accurately cleaves substrate RNAs.

According to the paper's authors, "recombinant RISC shows many of the properties of RISC purified from human or Drosophila melanogaster cells but also has surprising features. It shows no stimulation by ATP, suggesting that factors promoting product release are missing from the recombinant enzyme.

"The active site is made up of a unique Asp-Asp-His (DDH) motif," they noted. "In the RISC reconstitution system, the siRNA 5' phosphate is important for the stability and the fidelity of the complex but is not essential for the creation of an active enzyme. These studies demonstrate that Argonaute proteins catalyze mRNA cleavage within RISC and provide a source of recombinant enzyme for detailed biochemical studies of the RNAi effector complex."

The Scan

Wolf Howl Responses Offer Look at Vocal Behavior-Related Selection in Dogs

In dozens of domestic dogs listening to wolf vocalizations, researchers in Communication Biology see responses varying with age, sex, reproductive status, and a breed's evolutionary distance from wolves.

Facial Imaging-Based Genetic Diagnoses Appears to Get Boost With Three-Dimensional Approach

With data for more than 1,900 individuals affected by a range of genetic conditions, researchers compared facial phenotype-based diagnoses informed by 2D or 3D images in the European Journal of Human Genetics.

Survey Suggests Multigene Cancer Panel VUS Reporting May Vary Across Genetic Counselors

Investigators surveyed dozens of genetic counselors working in clinical or laboratory settings, uncovering attitudes around VUS reporting after multigene cancer panel testing in the Journal of Genetic Counseling.

Study Points to Tuberculosis Protection by Gaucher Disease Mutation

A mutation linked to Gaucher disease in the Ashkenazi Jewish population appears to boost Mycobacterium tuberculosis resistance in a zebrafish model of the lysosomal storage condition, a new PNAS study finds.