CytRx Subsidary Inks Informatics Deal with 3rd Millenium
CytRx said last week that its subsidiary Araios has signed a deal to establish a computing platform for its development programs with consulting firm 3rd Millennium.
CytRx recently established Araios to use RNAi to validate small molecule drugs for Type II diabetes and obesity. (See RNAi News, 9/19/03).
3rd Millennium will work with Araios on an informatics infrastructure, virtual library construction, homology modeling, and virtual screening workflow, said CytRx.
“Through our partnership with 3rd Millennium, we establish the scientific computing and informatics infrastructure necessary to conduct state-of-the-art molecular based drug discovery more rapidly and efficiently than we could do on our own,” Araios president Mark Tepper said in a statement.
Specific terms of the deal were not disclosed.
Acuity Receives $500,000 Ben Franklin Award
Ben Franklin Technology Partners of Southeastern Pennsylvania, a non-profit technology development organization, has granted Acuity Pharmaceuticals $500,000 to conduct preclinical activities on an siRNA therapeutic.
The ophthalmic company is currently developing RNAi-based treatments for age-related macular degeneration and diabetic retinopathy.
The award was part of a total $1.75 million being given to Southeastern Pennsylvania-based companies to develop their technologies, said Ben Franklin Techno- logy Partners.
Cold Spring Harbor Researchers Show RNA Binding Role for PAZ Domain
The PAZ domain of the Argonaute2 protein may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway, according to an article by researchers from Cold Spring Harbor Laboratory in the December issue of Nature Structural Biology. (Nat. Struct. Bio, Dec. 2003; 10: 12, 1026-1032).
Key components to RISC are Argonaute proteins, which contain the two characteristic domains PAZ and PIWI, according to the researchers.
“PAZ domains show low-affinity nucleic acid binding, probably interacting with the 3’ ends of single-stranded RNA,” they wrote in the article’s abstract. “PAZ can bind the characteristic two-based 3’ overhangs of siRNAs, indicating that although PAZ may not be a primary nucleic acid binding site in Dicer or RISC, it may contribute to the incorporation of siRNAs and miRNAs.”
UConn Researches Publish Data Showing Use of RNAi to Study Role of DCX in Rats In Utero
Researchers from the University of Connecticut have used RNA interference to demonstrate that doublecortin is required for radial migration in the rat cortex, according to a paper in the December issue of Nature Neuroscience. (Nat Neuro., Dec. 2003; 6: 12, 1277-1283).
“Mutations in the doublecortin gene (DCX) in humans cause malformation of the cerbral neocortex,” the researchers wrote in the article’s abstract.
“Paradoxically, genetic deletion of DCX in mice does not cause neocortical malformation.”
The researchers found that using short hairpin RNAs to interfere with the DCX protein in rats in utero resulted in both cell-autonomous and non-cell-autonomous disruptions in radical migration, and created two disruptions in neocortical development.
“In utero RNAi can therefore be effectively used to study the specific cellular roles of DCX in neocortical development and to produce an animal model of double cortex syndrome,” they noted in the abstract.
BioScience2004 Meeting to Include RNAi Symposium
The BioScience2004 — From Molecules to Organisms meeting has been scheduled and will include a multi-session forum called Genes: Regulation, Processing, and Interference.
Among the sessions to be included in the forum are Chromatin and Gene Regulation; Nuclear RNA Splicing and Processing; Transcription Regulation in Development and Signaling; DNA Repair and Checkpoints; Cell Cycle Control; and RNAi: How it Works and its Use as a Technology.
The RNAi mini symposium will feature Martin Gorovsky, from the University of Rochester; Phil Zamore, from the University of Massachusetts Medical School; Thomas Tuschl, from Rockefeller University; Tony Pawson, from the Samuel Lunenfeld Research Institute; and James Naismith, from the University of St. Andrews.
Additional speakers are to be announced.
BioScience2004 is being held on July 18-22 next year in Glasgow, UK at the Scottish Exhibition and Conference Centre (SECC).
Details about the event can be found at www.bioscience2004.org.
Preclinical Data on BCL-2 Antisense Drug Published
Researchers from the Regina Elena Cancer Institute and the University Hospital Zurich have published a report in the Nov. 20 issue of Oncogene demonstrating that the bcl-2/bcl-xL bispecific antisense oligonucleotide 4625 was able to inhibit bcl-2 expression and angiogenesis in two bcl-2 overexpressing clones derived from the M14 human melanoma line. (Oncogene, Nov. 20, 2003; 22: 52, 8441-8447).
In particular, the researchers noted in the article’s abstract, a reduction of hypoxia-induced VEGF secretion was observed after 4625 treatment, and the conditioned medium of bcl-2 overexpressing clones treated with the drug and exposed to hypoxic conditions resulted in decreased endothelial cell proliferation when compared to control cells.
The researchers also wrote that the control medium of 4625 antisense-treated bcl-2 transfectants inhibited in vivo vessel formation in matrigel plugs implanted subcutaneously in C57/B16 mice.
They said that the findings confirm the important role of bcl-2 in melanoma angiogenesis, and also show the potential of downregulating bcl-2 by antisense treatment to inhibit angiogenesis, and of 4625 as a drug therapy.
Lily, Isis Antisense Drug Inhibits Tumor Growth in Animal Models
Eli Lilly and Isis Pharmaceuticals said last week that their second-generation antisense drug LY2181308 significant inhibited tumor growth in animal models.
The companies said that the data support clinical development of the drug, which inhibits survivin expression.
“As an antisense drug, LY2181308 binds to survivin RNA, enabling it to inhibit the production of a target considered undruggable by traditional protein-binding approaches,” Richard Gaynor, vice president for cancer research and clinical investigation at Lilly, said in a statement. “The over-expression of survivin in a wide variety of tumors makes it an exciting target for drug development.