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Life Sciences
Small Molecule Microarrays: A New Forefront in Drug Discovery
Harvard References: 1633 and 2657Abstract: Scientists from the laboratory of Professor Stuart Schreiber at Harvard University have developed a novel method of printing small molecule libraries on glass microscope slides. The resulting small molecule arrays can be utilized in all facets of a drug discovery platform—from targeted libraries to bioassay development and screening. Additionally, the arrays can be prepackaged and sold as focused libraries, such as an ion channel or GPCR set. Small molecule arrays represent a next-generation platform for drug discovery that will allow bench top library screening.
Contact: Laura Brass, laura_brass@harvard.edu
First-In-Class Isoform Specific HDAC Inhibitors: Lead Compounds for the Treatment of Cancer and Neurodegenerative Diseases
Harvard References: 2436, 2672, 2673Abstract: Researchers at the Broad Institute of Harvard University (Stuart Schreiber) and the Dana Farber Cancer Institute (Drs. Ken Anderson and Jay Bradner) have discovered a novel set of first-in-class HDAC inhibitors that target a specific HDAC isoform--HDAC6. Recent studies have demonstrated a primary role for HDAC 6 in both aggresome-mediated diseases (cancer and neurodegenerative diseases) as well as microtubule-associated cell motility (metastatic cancer). The advantage of these small molecules over other HDAC inhibitors currently in development is their specificity and efficacy at low nanomolar concentrations; thus providing for a lower toxicity profile in human subjects.
Contact: Laura Brass, laura_brass@harvard.edu
Mu Opioid Peptidomimetics: Lead Compounds for the Treatment of Pain
Harvard References: 1472 and 2129Abstract: Although peptides have shown some promise in clinical trials as therapeutic agents, their success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Researches at Harvard University have overcome these limitations with the advance of peptidomimetics--a system for the production of modified chemical compounds capable of mimicking the structural and or functional properties of peptides. Using this approach they have generated nonpeptidic ligands to a key receptor involved in pain relief, the mu opioid receptor (MOR). Selection assays using compounds of this series exhibited was 600% more selective for MOR than the delta opioid receptor (DOR) and kappa opioid receptor (KOR), respectively. This selectivity profile of the lead compounds along with the synthesis platform has far-reaching implications for the discovery of next-generation therapeutics for the treatment of pain.
Contact: Laura Brass, laura_brass@harvard.edu
The Next Generation of Proteasome Inhibitors: Beyond Velcade™
Harvard References: 1087, 2326, 2342, 2463, 2549Abstract: Proteasome inhibition offers considerable promise in the therapy of a number of types of diseases, such as cancer and neurodegenerative diseases. One such proteasome inhibitor, Velcade™, is currently marketed for treatment of multiple myeloma by Millennium Pharmaceuticals. Despite the success of Velcade™, proteasome inhibition has not fulfilled the promise it demonstrated. For example, animal studies indicated that bortezomib injected intravenously leaves the vascular compartment within minutes, rendering correlations between plasma concentrations and proteasome inhibition, drug toxicity, and clinical activity difficult. Newly discovered proteasome inhibitors, such as the natural products salinosporamide and lactacystin, hold considerable promise as safe and efficacious next-generation agents—likely hitting different proteasome targets. Researchers at Harvard University have discovered novel synthetic pathways to these natural products and their analogs that proceed in fewer steps and much greater overall yield than current methods. Furthermore, the compounds demonstrate potent efficacy in both cellular assays and animal models of cancer and neurodegenerative diseases.
Contact: Laura Brass, laura_brass@harvard.edu
Applied Sciences, Computer Science, Physical Sciences and Engineering
Medical Devices and Related Applications
A Novel Biologically Selective “Smart” Surgical and Diagnostic Medical DeviceApplication and Benefits: (a) Surgical instruments that can bind to and remove analytes, cells, and tissues with molecular specificity and sensitivity – for example, a catheter capable of detecting and removing athlerosclerotic lesions. (b) Diagnostic tool for specific blood or urine markers – for example, instant diagnosis of heart attack. (c) Other clinical applications may leverage the novel versatile polymer films to regulate analyte concentrations in solution or provide localized delivery of drugs or analytes, while non-clinical applications may generate label-free electrochemical CMOS microarrays and proteomic chips. The devices are highly sensitive and specific in their reversible binding.
Innovation: Molecular sensitivity is generated through dopants (e.g., ligands, receptors, ions, surfactants) on a conductive polymer film functionalized to the surface of a surgical instrument. Improvements over the prior art include the novel use of reversible polymer films with a medical device substrate, significantly enhanced fabrication protocol, improved charge transfer kinetics, and conductive polymer films sensitive to a wide dynamic range of binding events (e.g., nanoscale range). Doped ligands or receptors may include proteins, enzymes, analytes, biomolecules, DNA, mRNA, fatty acids, drug compounds or synthetic peptides
Contact: Michal Preminger, michal_preminger@harvard.edu, Harvard Reference: 2774
Novel Nanopore Sequencing of Nucleic Acid: Towards the $1000 Genome
Application and Benefits: DNA sequencing that is very inexpensive, label-free, reagent-free, and extremely fast. This technology could be a significant enabler of personalized medicine
Innovation: The method is based on “passing” DNA strands through nano-pores that are outfitted with carbon nanotubes which can “read” the changes in electrical properties of the various nucleic acids at extraordinary speeds. Development of this technology has been funded by NIH and has resulted in a comprehensive cluster of patents.
Contact: Bob Benson, robert_benson@harvard.edu, Harvard Reference: 637
Enhanced MRI Rivals the Imaging Performance of PET by Using Hyper-polarized Nanoparticle Imaging Agents
Applications and Benefits: Enables real-time MRI imaging at resolutions rivaling those of PET scans (a $2B market in 2004, growing at 11.5% annually)…but at lower cost, improved patient safety, and the ability to leverage the much wider availability of MRI equipment. The technology can be used as a diagnostic for very specific diseases / tumors and to track effectiveness of drugs and cell therapies (drug discovery and efficacy).
Innovation: Novel Nanoparticle Imaging Agent (NIA) can be attached to biologically relevant macromolecules (e.g. Monoclonal Antibodies) to make long-life Combination Products (nanoparticle + biologic) that can be tracked through the body using MRI. The nanoparticles are biologically inert and the NIA has long life for imaging over time.
Contact: Alan Gordon, alan_gordon@harvard.edu, Harvard Reference: 2572, 2620, 2648
Ad-hoc, Adaptive Wireless Sensor Networks for Medical and Monitoring Devices
Applications and Benefits: Enables sensor network applications that require ad-hoc interactions, real-time configuration, data analysis, and smart network decisions. For example, medical sensor devices have been deployed with this technology to collect heart rate, oxygen saturation, and EKG data and relay this information over a short-range (100m) wireless network to any number of receiving devices, including PDAs, laptops, or ambulance-based terminals. The data can be displayed in real time and integrated into the developing pre-hospital patient care record. The sensor devices can raise an alert condition when vital signs fall outside of normal parameters, signaling adverse changes in patient status to a nearby EMT or paramedic.
Innovation: Wireless network architecture and software that allows for adaptive, ad-hoc communication between monitoring / medical devices.
Contact: Alan Gordon, alan_gordon@harvard.edu, Harvard Reference: 2337, 2425
Applications in Computer Science / IT
Opinion Polling in Real-time Through Content Analysis of Unstructured Text
Applications and Benefits: Unique method of computerized content analysis that provides real-time categorization of unstructured text documents over time. The method provides accurate estimates of various types of “opinions” expressed in large numbers of on-line documents – and tracks how those opinions change in real-time. The effectiveness of this approach has been demonstrated through several examples, including tracking the daily opinions of millions of people about candidates for the 2008 presidential nominations in online blogs.Innovation: With a small subset of documents hand coded into categories, our approach provides accurate estimates of the percentage of documents in each category in a larger population. This method does not require random samples and corrects for the human error inherent in hand-coding.
Contact: Alan Gordon, alan_gordon@harvard.edu, Harvard Reference: 2916
Secure On-line Auctions Protect Against Fraud in Large Financial Transactions
Applications and Benefits: Reduce fraud by keeping bids secret and encourage honest bidding by using advanced auction models. This is of particular interest to procurement professionals at large corporations and financial institutions using sealed bid auctions.
Innovation: The software protocols completely hide the value of all bids until the auction's close -- even from the auctioneer -- and ensure correctness and provide trust. After the auction, the auctioneer opens the bids but can still announce an outcome and prove it correct without revealing any bid to anyone else. The protocols and software support auctions of one or many identical items and extend to facilitate real-time cryptographic securities exchanges.
Contact: Alan Gordon, alan_gordon@harvard.edu, Harvard Reference: 2693, 2930, 2931
Applications in Energy, Physical Sciences, Engineering
Low Temperature, Highly Scalable, Cost Effective Solid Oxide Fuel Cells (SOFCs)
Applications and Benefits: SOFCs that can operate at low temperatures (300 ºC to 600 ºC vs. the current ~1000 ºC) are highly desirable to the fuel cell industry because they will dramatically increase the number of practical applications for SOFCs and lower the cost of materials. Our low temperature SOFCs offer significantly enhanced performance, greatly reduced form factors, and can provide a wide range of power outputs – thus making them suitable for both stationary and transportation applications. Applications in portable electronics may also be feasible.Innovation: These micro-scale fuel cells use novel nano-fabrication technologies based on well-proven semiconductor processes. The resulting devices enable applications where a small form-factor is desirable (such as mobile power units), yet the devices are easily scalable to deliver virtually any wattage. A related invention, the “accelerated oxygen exchange” process, can significantly improve performance of any SOFC.
Contact: Daniel Behr, daniel_behr@harvard.edu, Harvard Reference: 2707, 2878, 2917
Hydrogen Production via Scalable Bioengineered Yeast Systems
Application and Benefits: Production of Hydrogen (H2) from biomass through a novel engineered yeast system that is scalable and efficient. This is of particular interest to emerging H2 markets over the next 5 to 10 years, namely broad industrial and small-scale transportation opportunities (e.g., off-road vehicles such as forklifts, scooters, utility vehicles, hydrogenation of biofuels, hydrogen/natural gas blends). The Harvard system enables the use of distributed hydrogen as an alternative fuel source in HPVs (hydrogen powered vehicles). The system could also be of use in current H2 applications ($2B market) such as semiconductor manufacturing, food processing, metal processing, float glass, specialty chemicals and pharmaceuticals.
Innovation: The invention applies aggressive engineering of metabolic pathways and reducing complexes to create a yeast microenvironment capable of producing hydrogen from glucose at theoretical maximum levels (approaching >50 kg hydrogen/ton of biomass). This is achieved by (a) engineering new pathways in yeast to generate stronger biological reducing agents, (b) constructing artificial organelles (microenvironments within cells) to enhance the H2 production, and (c) engineering different organisms (both yeast and bacteria) that are each optimized for performing particular reactions so that an appropriate mixture of organisms will form a symbiotic system to produce hydrogen.
Contact: Michal Preminger, michal_preminger@harvard.edu, Harvard Reference: 2846
Novel Microbial Fuel Cell: Electricity From Dung
Application and Benefits: This is a low cost microbial fuel cell (MFC) particularly suited for applications where electrical power is needed in remote, off-grid locations. For example MFCs can power LEDs that illuminate roads or demarcate the edges of rivers and streams. The MFC has obvious applications in third world countries. MFCs are portable, well-suited to aqueous environments, and can be maintained without reliance on advanced technology or expensive components. MFCs are highly efficient (>50%) and can operate virtually anywhere and in virtually any weather condition. The MFCs are environmentally “green” and very safe to use. This device has an extremely long life – it should operate for ten years continuously at a cost of 0.8 cents a day with modest maintenance, such as cleaning of the electrodes every three years. The components used to construct a MFC are inexpensive, costing a total of $5 USD.
Innovation: A microbial fuel cell (MFC) is a device that converts chemical energy to electrical energy by the catalytic reaction of microorganisms. Harvard developed a novel, low-cost MFC capable of delivering high power, high-efficiency energy. The MFC takes advantage of an easily accessible and ubiquitous carbon source. The organic carbon source can be metabolized by a wide number of microbial types and Harvard has identified many microbial types that can grow on a fuel cell’s anode and stimulate power production. Thus, using extremely simple electronics, the MFC can be configured to select for different microbial types, depending on the carbon source being used
Contact: Laura Brass, laura_brass@harvard.edu, Harvard Reference: 2763
Instrument for Rapid, Real-time Measurement of Thermal Properties of Materials
Application and Benefits: Ultra-fast, high precision measurement of thermal properties of materials using only thin films of the materials. Measurements include thermal conductivity and differential scanning calorimetry. Because the measurement is done using novel micro-scale sensors, many measurements can be done at one time to quickly characterize thermal properties as a function of material composition, thickness, etc. This is of particular use for companies that are synthesizing new materials or new alloys, or for anyone involved in thin-film deposition.
Innovation: This instrument relies on a novel micro-scale sensor design. Arrays of these sensors can be cost-effectively incorporated into any substrate onto which materials under study can be deposited. Once the material is deposited, the sensors capture information on thermal properties very rapidly.
Daniel Behr, daniel_behr@harvard.edu, Harvard Reference: 2755