Signaling for Stem Cells
By comparing two signaling networks, scientists, in a recent issue of Science, report a specific pathway critical for inducing human bone-marrow stem cells to differentiate into bone-forming cells Further research could be beneficial for increasing the precision with which stem cells can be persuaded to differentiate into specific cell types needed for tissue regeneration and engineering, the researchers write. The group used mass-spectrometry-based proteomics to compare the hundreds of proteins that are modified by phosphorylation in response to signals from two related receptor tyrosine kinases, which are receptors that regulate a variety of cellular processes by triggering multiple signaling cascades. The epidermal growth factor (EGF) receptor induced the human mesenchymal stem cells that the researchers studied to differentiate into bone-forming cells. Platelet-derived growth factor (PDGF) receptor did not induce bone-forming cells from the same stem cells, thus highlighting the fact that closely related signals often lead to very different cellular outcomes. The proteomic approach allowed the researchers to pinpoint a subtle difference in the two signals that accounted for the distinct biological responses.
Survey Seeks Top Scientists for a Study of Research Innovation
Who's doing the most innovative and important research in the fields of human genetics and nanotechnology? A team of US and European researchers will be asking that question through a survey that 1,200 leading scientists, industrial researchers, journal editors, and research program directors will be receiving this month. The questionnaire is part of an 18-month study to determine what factors lead to especially innovative and important research, with a goal of determining what institutions might do to foster it. The Project on Creative Capabilities and the Promotion of Highly Innovative Research (CREA) is being carried out by researchers at the Fraunhofer Institute for Systems and Innovation Research (ISI) in Germany, the Technology Policy and Assessment Center (TPAC) in the School of Public Policy at the Georgia Institute of Technology and Sussex University's Science and Technology Policy Research Unit in the United Kingdom. Using the results of the survey, the research team plans to identify about 60 scientists and research teams on both sides of the Atlantic that are responsible for creative research that has produced innovative breakthroughs in human genetics and nanotechnology. Using in-depth interviews with the individuals and systematic studies of scientific productivity, the CREA study will then attempt to determine the factors, both personal and environmental, that helped those researchers work so effectively.
Collaboration on Biomarker-Based Diagnostic Products
Compugen, Tel Aviv, Israel, announced a collaboration agreement with Ortho-Clinical Diagnostics Inc., a Johnson & Johnson company, for the development and commercialization of immunoassay diagnostic markers. During the initial phase of the agreement, Ortho-Clinical Diagnostics will have the right to select up to nine biomarkers for development from Compugen’s portfolio, with the parties then collaborating on the initial clinical validation of the selected biomarkers. Under the agreement, successfully validated biomarkers will be developed into products and commercialized by Ortho-Clinical Diagnostics, with Compugen receiving milestone payments and license fees for each commercialized biomarker, in addition to revenue-based royalties. Compugen’s discovery process relies on the comprehensive predictive analysis of the human proteome provided by the company’s LEADS platform. The results of this analysis are used with a variety of discovery engines, each designed to identify novel proteins with specific desired characteristics from the vast number predicted by the discovery process.
Chemistry for Oligonucleotide-Based Therapeutics
Topigen Pharmaceuticals Inc. introduced a new chemistry technology called FANA (Fluoro Arabino Nucleic Acid), which the company says is unique among oligonucleotide chemistries. The platform uses an important modification in the sugar unit of the oligonucleotide chain that renders the FANA structure (arabinose sugar) much more stable than the normal ribose structure (RNA). Masad Damha, PhD, inventor of FANA and professor of chemistry at McGill University, Montreal, Canada, said the platform significantly improves the functionality of oligonucleotides for gene targeting and silencing and offers an alternative to the traditional antisense and RNAi approaches. In a series of studies comparing available gene modulating chemistries, FANA showed an improvement in target affinity and duration of gene response while improving efficacy and safety. FANA, says Damha, also significantly enhances nuclease resistance, providing lower dosage requirements and the potential for improved systemic administration. The unique characteristics of the FANA chemistry may be advantageous for a wide variety of therapeutic gene-modifying applications, including topical and systemic administration. TOPIGEN is currently developing a novel, multitargeted drug product for COPD that uses FANA technology. Delivered via aerosol, the product (PD-3) is designed to inhibit gene expression pathways linked to the progressive airway remodeling associated with the disease. The drug candidate is scheduled to enter clinical trials in 2007.
Stem Cell Therapies Receive Major Funding
Osiris Therapeutics, which develops adult stem cell therapies, announced that the company received $50 million in funding to support and advance three stem cell therapies currently in human trials. Osiris uses stem cells obtained from adult tissue donated by living volunteers that are then grown in culture to very high numbers, allowing a single donor's cells to treat hundreds of patients. Currently, the company has three ongoing stem cell clinical trial programs working to commercialize treatments for heart attacks, knee repair, and graft-versus-host disease (GvHD) for patients undergoing bone marrow transplants. Provacel, a formulation of stem cells to repair damaged heart tissue following heart attack, is enrolling patients in a phase I clinical trial. Most recently, Osiris won FDA approval to begin a phase I/II study for Chondrogen, an injection of stem cells formulated to repair damaged tissue in the knee joint and prevent the progression of arthritis. The GvHD treatment Prochymal is in phase II clinical trials and is the only stem cell product with FDA fast-track status. The M.D. Anderson Cancer Center, Houston, is participating in the trial.
Two New High-Sensitivity Western Blot Substrates
Millipore, Billerica, Mass., today announced the availability of two new, high sensitivity chemiluminescent substrates for Western blotting applications. The inexpensive Immobilon Western HRP and AP Chemiluminescent Substrates provide high signal response at mid-femtogram levels. Primarily used in Western and dot/slot/spot blotting applications, each versatile substrate has a high signal intensity to facilitate the detection of both high and low abundance proteins. The Western HRP and AP Chemiluminescent substrates use two- to fivefold less primary and secondary antibodies than traditional, low-sensitivity substrates. As a result, antibody consumption is decreased significantly and reagent costs are reduced. Available in ready-to-use formats, the two substrates are compatible not only with polyvinylidene fluoride (PVDF) and nitrocellulose membranes, but also commonly used buffers and blocking reagents.
By Elizabeth Tolchin