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Technology Name
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Scientist
1749
Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity. Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is...

Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity.
Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is highly diffusive and buoyant. Currently, hydrogen is stored physically as a gas, requiring high-pressure tanks, or in liquid form at cryogenic temperatures, both methods require high energy input. Proposed chemical storage systems are based on relatively expensive materials, suffer from poor regeneration after hydrogen release and require elevated temperatures and pressures.
The presented technology utilizes inexpensive and abundant organic compounds that generate hydrogen gas during a chemical transformation. Hydrogen release and the regeneration of the original compound are performed in mild conditions using the same catalyst. This system is a promising candidate to be the basis of compact and cost-effective chemical hydrogen storage platforms.

Applications


  • High potential hydrogen storage capacity (6.6 wt%)
  • Inexpensive and readily available hydrogen carriers (aminoalcohols)
  • Relatively mild release and regeneration conditions

  • Advantages


    • Hydrogen-fueled systems, including fuel cells
    • High capacity hydrogen storage systems

    Technology's Essence


    The technology is based on aminoalcohols that are catalytically converted to cyclic dipeptides, while forming hydrogen gas, using a ruthenium pincer catalyst. Peptide hydrogenation, using the same catalyst, regenerates the aminoalcohol. The same method can be applied with diaminoalkanes and alcohols as well.
    The reaction requires a relatively low organic solvent volume, a catalytic amount of base (KOtBu) for the in situ generation of the active catalyst and mild reaction conditions in terms of hydrogen pressure (50 bar) and temperature (~100 oC). Repetitive cycles of the dehydrogenation-hydrogenation reactions can be performed without adding new catalyst, while maintaining high percentages of aminoalcohol conversion.

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    • Prof. David Milstein
    1704
    Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions. The search for such cure is tremendously hindered by the...

    Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions.
    The search for such cure is tremendously hindered by the unmet need for a reliable biochemical biomarker for nGD.
    The present invention identifies the glycoprotein non-metastatic B (GPNMB) as a potential powerful nGD biomarker for use in early diagnosis, determination of disease severity, as well as a straight forward readout in clinical and preclinical experiments.

    Applications


    Diagnosis and drug development for neuropathic GD

    Advantages


    Straight forward diagnostic tool – based on standard biochemical assays
    Relatively simple clinical procedure – samples are collected from CSF and not brain
    High sensitivity – for the diagnosis of disease severity
    Compatible with preclinical experiments

    Technology's Essence


    Prof. Futerman and his team preformed a quantitative global proteomic analysis (using LC-MS/MS) of cerebrospinal fluid (CSF) samples from four patients with Type 3 GD, to identify mis-regulated proteins, compared with healthy subject.
    Glycoprotein non-metastatic B (GPNMB), a protein that was previously associated with several lysosomal storage disorders, exhibited very high levels (a 42-fold increase) in the CSF of type 3 GD patients.  Two peptides were identified from GPNMB, both located in the non-cytosolic domain, suggesting that GPNMB is cleaved and secreted into the CSF from the brain. LC-MS/MS results were validated by ELISA and by western blot analysis in CSF and in human brain samples.
    Several proof of principle experiments were conducted in order to prove the validity of using GPNMB as a biomarker for monitoring disease state and treatments efficacy in neuropathic GD in patients and mouse models:
    GPNMB levels were shown to be correlated with the severity of type 3 Gaucher’s disease patients, as measured by lower IQ score and lower score in Purdue Pegboard test, assessing eye-hand coordination. In addition, using conduritol b epoxide (CBE)-injection based mouse model that simulate different severities and recovery periods, it was shown that GPNMB levels rapidly rise or decline to reliably reflect progress/remission states of the diseases.

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    • Prof. Anthony H. Futerman
    1800
    A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses. The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt...

    A new software tool used for the removal of artifacts from transcranial magnetic stimulation (TMS) triggered electroencephalography (EEG) was developed by the group of Prof. Moses.

    The combined use of TMS with EEG allows for a unique measurement of the brain's global response to localized and abrupt stimulations. This may allow TMS-EEG to be used as a diagnostic tool for various neurologic and psychiatric conditions.

    However, large electric artifacts are induced in the EEG by the TMS, which are unrelated to brain activity and obscure crucial stages of the brain's response. These artifacts are orders of magnitude larger than the physiological brain activity, and persist from a few to hundreds of milliseconds. However, no generally accepted algorithm is available that can remove the artifacts without unintentionally and significally altering physiological information.

    The software designed according to the model along with a friendly GUI is a powerful tool for the TMS-EEG field. The software has tested and proven to be effective on real datasets measured on psychiatric patients.

    Applications


    • TMS triggered EEG diagnostics

    Advantages


    • Easy to use software with a GUI
    • Exposes the full EEG from the brain

    Technology's Essence


    The new software tool is based on the observation that, contrary to expectation, the decay of the electrode voltage after the TMS pulse is a power law in time rather than an exponential. A model based on two dimensional diffusion of the accumulated charge from the high electric
    fields of the TMS in the skin was built. This model reproduces the artifact precisely, including the many perplexing artifact shapes that are seen on the different electrodes. Artifact removal software based on this model exposes the full EEG from the brain, as validated by continuously reconstructing 50Hz signals that are the same magnitude as the brain signals.

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    • Prof. Elisha Moses
    1751
    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets. The present...

    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets.
    The present discovery elucidates the pathway by which argininosuccinate synthase (ASS1) down-regulation confer cancer progression. It shows that decreased activity of ASS1 in cancers supports proliferation by linking excess aspartate to pyrimidines synthesis. Importantly, these studies highlight Citrin (a mitochondrial aspartate transporter) inhibition as a potential method to decrease aspartate levels and selectively target this metabolic pathway in ASS1 depleted cancers.

    Applications


    • Targeted Treatment for ASS1 depleted cancers.

    Advantages


    • Targeted therapy, against a well defined pathway, increases the prospects for success.
    • Selective – targeting cancer metabolic dependency minimizes the chances for healthy cells damage that lead to side effects.

    Technology's Essence


    Cancer cells hijack and remodel existing metabolic pathways for their benefit in what is termed the Warburg effect. Researchers from Dr. Ayelet Erez's lab, at the Weizmann institute of Science, have delineated the metabolic benefit(s) conferred by loss of ASS1 to cancers. In agreement with previous experience, they found that ASS1 deficiency has an additional arginine- independent effect that is directly related to its substrate, aspartate.
    By focusing on the relevant physiological and pathological model systems, it was found that ASS1 deficiency-mediated increase in aspartate levels lead to excessive proliferation through pyrimidine synthesis. The link between the two is provided by CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, dihydroorotase complex) and the mTOR signaling pathway.
    Importantly, the present inventors have found that blocking Citrin, the mitochondrial aspartate transporter, rescues cell proliferation by reducing aspartate levels. Citrin may thus serve as a strong candidate for targeted therapy of ASS1 depleted cancers.   
    Supporting this model, retrospective survival analysis of several cancers reveal that cancers with both decreased ASS1 expression and high Citrin levels have a trend for significantly worse prognosis.

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    • Dr. Ayelet Erez
    1712
    • Prof. Yechiel Shai
    1802
    A new signal processing tool for the detection of pulses travelling through media with complex or unknown dispersion properties was developed by the group of Prof. Gal-Yam, originally for detecting radio bursts in astronomical observations. Pulses are applied in various fields such as oil & gas...

    A new signal processing tool for the detection of pulses travelling through media with complex or unknown dispersion properties was developed by the group of Prof. Gal-Yam, originally for detecting radio bursts in astronomical observations.
    Pulses are applied in various fields such as oil & gas exploration, detection (e.g. sonar, lidar and radar) and communication. When pulses pass through dispersive media, the arrival times at the detector of different frequency components may differ, and as a result the pulse may become degraded (e.g. transformed to a longer pulse with reduced intensity), even to the level of becoming indistinguishable in terms of signal to noise. This problem becomes even more challenging when detecting short pulses that travel through complex or unknown media.
    The new method presented here provides a proven and efficient solution that can be applied for different scenarios where short pulses dispersed by complex media are used. 

    Applications


    • Detection and surveying technologies- sonar, lidar, radar etc

    Advantages


    • Efficient, requires limited computational resources
    • Generic, can be applied to various setups
    • Easily implementable into existing systems

    Technology's Essence


    The method includes obtaining an input array of cells, each indicating an intensity of a frequency component of the signal at a representative time. A fast dispersion measure transform (FDMT) is applied to concurrently sum the cells of the input array that lie along different dispersion curves, each curve defined by a known non-linear functional form and being uniquely characterized by a time coordinate and by a value of the dispersion measure. Application of FDMT includes initially generating a plurality of sub-arrays, each representing a frequency sub-band and iteratively combining pairs of adjacent sub-arrays in accordance with an addition rule until all of the initially generated plurality of sub-arrays are combined into an output array of the sums, in which a cell of the output array that is indicative of a transmitted pulse is identified.

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    • Prof. Avishay Gal-Yam
    1753
    The Chiral Induced Spin Selectivity (CISS) effect, discovered in recent years by Prof. Ron Naaman from the Weizmann Institute of Science, implies that electrons transferred through chiral molecules possess a specific spin orientation. Hence, the molecular chirality and electron spin are correlated.A...

    The Chiral Induced Spin Selectivity (CISS) effect, discovered in recent years by Prof. Ron Naaman from the Weizmann Institute of Science, implies that electrons transferred through chiral molecules possess a specific spin orientation. Hence, the molecular chirality and electron spin are correlated.
    A team of researchers lead by Prof. Naaman have been investigating the CISS effect in different systems. They found that the high efficiency of many natural multiple electron reactions can also be attributed to spin alignment of the electrons involved.
    The present innovation looks at hydrogen production through water electrolysis, showing that when using anodes coated by chiral molecules the efficiency of the electrolysis process increases by 30% compared to using uncoated, regular electrodes.

    Applications


  • Control of electron spin
  • Significant reduction of over-potential in spin sensitive electrochemical reactions
  • Efficient electrochemical processes
  • Minimum side reactions

  • Advantages


     

    Technology's Essence


    Spin selective electrodes made from standard electrode material are coated with chiral molecules. These coated electrodes were used for electrolysis of water and showed superior efficacy compared to standard un-coated electrodes, by reduction of the over-potential required for the process. This is explained by the spin selective electron conduction through the chiral layer:

     

     

     

    Hydrogen production as a function of time for (A) the chiral molecules and (B) for the achiral molecules. The potentials in the brackets refer to the over-potential compared to DNA coated electrode. The measurements were conducted at the Eapp for each of the molecules.

     

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    • Prof. Ron Naaman
    1670
    A method for selective extraction of precious and rare metals has been developed at the Weizmann Institute. This method allows the efficient and environmentally benign recovery of precious materials that are currently discarded of in large quantities from spent catalysts (automotive and industrial)...

    A method for selective extraction of precious and rare metals has been developed at the Weizmann Institute. This method allows the efficient and environmentally benign recovery of precious materials that are currently discarded of in large quantities from spent catalysts (automotive and industrial) from industrial processes (particularly in the electronic industry).

    Prof. Igor Lubomirsky’s novel process is based on volatilization for selective extraction of precious and rare metals using benign metal salts, rather than dangerous chlorine gas as a chlorinating agent. The new process requires relatively low temperatures and is free from hazardous waste, among its additional advantages over conventional methods.

    We believe that this efficient technology is key to increased reclaimed precious metals output, potentially resulting in the reduction of the demand for primary rare metals.

    Applications


    ·           Recycling precious metals from spent items, e.g. platinum group metals from catalytic convertors


    Advantages


    ·         No toxic input – chlorides are used rather than chlorine gas.

    ·         No hazardous waste is generated in the process.

    ·         Mild conditions. High-temperature furnaces and equipment are not required.

    ·         Relatively simple setup in comparison to conventional ones.

    ·         Small scale plants are economically viable.


    Technology's Essence


    Prof. Igor Lubomirsky and his group developed a novel method for the recovery of PGM from spent catalysts that can be applicable for other spent systems as well.

    The method comprises of crushing the spent catalyst to obtain a catalyst particulate material with g a predetermined grain size and reacting it with chlorine containing salts rather than pure chlorine gas in a furnace at relatively low temperatures (900oC, far below the temperature required in the conventional volatilization method). This is followed by cooling the volatile PMG chloride product converting it into solid phase metal.

     

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    • Prof. Igor Lubomirsky
    • Prof. Igor Lubomirsky
    1722
    Our technology provides a new type of oxidative cleavage reaction of organic compounds with highly selective product formation.Polyoxometalate (POM) catalysts have become well-known for their utility and diversity in specific reactions. Through the elucidation of POM catalytic pathways, greater...

    Our technology provides a new type of oxidative cleavage reaction of organic compounds with highly selective product formation.
    Polyoxometalate (POM) catalysts have become well-known for their utility and diversity in specific reactions. Through the elucidation of POM catalytic pathways, greater versatility has been achieved. This technology is one such application of a novel POM catalyst and is exploited to cleave carbon-carbon double bonds in alkenes (olefins) through an aerobic oxidation reaction. Oxidation reactions are of particular interest because they are difficult to achieve on an industrial scale while maintaining “green” chemistry practices. [1]

    --------------------------------------------------------------------------------
    [1] Green Chem., 2007, 9, 717-730

    Applications


    • As a novel catalyst in industrial organic chemistry processes
    • Sold as a stand-alone catalyst for laboratory or individual use

    Advantages


    • Environmentally friendly oxidation reaction
    • Easy catalyst regeneration

    Technology's Essence


    Our approach is motivated by societal considerations that demand environmentally benign and sustainable solutions for oxidative reactions. As such, we have developed a scheme to react NO2 with a transition-metal-substituted POM which yields a metal-nitro intermediate that is competent for forming the precursors for oxidation with molecular oxygen, O2, to have a final product of ketones and/or aldehydes, and regenerate the POM catalysts.[1]
    This method has preference towards di/tri-substituted alkenes. High yields of ketones or aldehydes have been produced and the POM catalyst is regenerated without further oxidation to carboxylic acids, as is typical with other oxidative catalysts.
    The selective cleavage of carbon-carbon double or triple bonds with metal-nitro or metal-nitrito compound has not been reported. This exciting new discovery could lead to a wide variety of organic reactions not previously possible, along with revolutionary green oxidative chemistry techniques.

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    [1] J. Am. Chem. Soc., 2014, 136(31), pp10941-10948 

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    • Prof. Ronny Neumann
    1673
    CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical...

    CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical importance in patients with chronic obstructive pulmonary disease (COPD), trauma, burn wounds, sepsis, or in patients requiring ventilation. The infections are currently treated with antibiotics, which rapidly become inefficient as resistant bacteria strains arise. The present technology suggests a novel therapeutic approach for the prevention and treatment of bacterial lung infection in susceptible populations, especially CF patients

    Applications


    • Alternative treatment for bacterial lung infections.
    • A prophylaxis for patients susceptible to bacterial lung infections

    Advantages


    • A novel therapeutic approach to prevent or cure bacterial lung infection.
    • The new therapy is based on reinforcement of the physiological innate immunity rather than on antibiotics.
    • The new therapy can be easily administered, via inhalation.
    • FTY720, a SPH analog, is already in clinical use for treating multiple sclerosis.

    Technology's Essence


    Sphingosine (SPH), a natural bactericidal agent which acts as a part of the human innate immune system in the skin, was found to be an effective treatment and prophylaxis for bacterial lung infections in cystic fibrosis (CF) mice. The new technology is based on the discovery that both CF human patients and CF mice display reduced rates of SPH in the airways. Moreover, normalizing SPH levels by inhalation prevents or cures the infections in CF mice, thus rendering SPH and its analogs a potent therapeutic agent for CF patients, an alternative to antibiotics.

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    • Prof. Anthony H. Futerman
    1772
    MTCH2 as a novel target for the treatment of obesity.Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-...

    MTCH2 as a novel target for the treatment of obesity.
    Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer, some of the leading causes of preventable death. Physicians and patients alike consider the weight-loss efficacy of the current therapeutics to be unsatisfactory. Therefore, there is an unmet need for innovative options that are at once safe and efficacious, and allow the patient to maintain weight loss.
    The present invention describes the identification of Mitochondrial Carrier Homolog 2 (MTCH2) as a novel player in muscle metabolism and the therapeutic potential of inhibiting MTCH2 for the treatment of diet-induced obesity and diabetes.

    Advantages


    • A fresh approach for targeting weight-related disorders
    • Direct effect on metabolism instead of indirect mechanisms of current therapeutics which target appetite modulation.
    • Protection from diet-induced obesity can be used as a prevention treatment for people with a tendency for weight gain.  

    Technology's Essence


    MTCH2 functions as a receptor-like protein for the pro-apoptotic BID protein in the mitochondria.
    MTCH2 was identified as one of six new gene loci associated with Body Mass Index (BMI) and obesity in humans suggesting that MTCH2 may also play a role in metabolism.
    MTCH2 was recently shown by the Gross’s lab to also function as a repressor of   mitochondria oxidative phosphorylation (OXPHOS) in the hematopoietic system.
    Deletion of MTCH2 in skeletal muscle increases mitochondrial OXPHOS and mass, and increases capacity for endurance exercise. In addition, loss of MTCH2 increases mitochondria and glycolytic flux in muscles as measured by monitoring pyruvate and lactate levels.
    MTCH2 knockout mice are protected from diet-induced obesity, hyperinsulinemia, and are more prone to weight loss upon caloric restriction.
    Therefore, the association of MTCH2 with mitochondrial function offers a potential novel target for muscle metabolism modulation in the fight against metabolic disorders such as obesity and diabetes.

     

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    1733
    The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change...

    The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change their location. Today, there is a widely recognized need to identify novel sequences which regulates nuclear translocation.
    Recently, Prof. Zeger and his team discovered a new level of regulation to stimulated transcription. They showed that ?-like importunes are central mediators of nuclear translocation of signaling proteins. Furthermore they identified the site of interaction and designed accordingly a peptide which was found to prevent nuclear translocation.
    This technology presents peptides with the potential of treating inflammatory and immune disease by regulating (prevent or promote) the translocation of proteins into the nucleus.

    Applications


    • Inflammation
    • Immune diseases

    Advantages


    • Effective
    • Safe

    Technology's Essence


    The researchers found that ?-like importins play a key role in JNK and p38 translocation. They also found that the translocation of these MAPKs is mediated by the formation of either Imp3/Imp7/MAPK or Imp3/Imp9MAPK heterodimers. Most importantly, the researchers identified the site in p38 that mediate the interaction with Imp7 and Imp9 and showed that the important sequence lies within residues 20-30 of p38?. Subsequently they synthesized a 14 amino acid myristoylated peptide based on the sequence of residues 21-34 of p38?. When it was applied to HeLa cells prior to stimulation, it prevented the nuclear translocation and Imp7/9 interaction of the MAPKs. Since the peptides of this technology are able to specifically inhibit the nuclear activities of p38 (such as inflammatory activities) without modulating their cytoplasmic activities, these peptides may serve as a therapeutic agent for inflammatory and apoptosis related diseases without having side effect.

     

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    • Prof. Rony Seger
    1684
    Gaseous energy sources such as hydrogen and natural gas (predominantly methane) encompass an intrinsic transport problem because of their volatility and flammability. Adsorption of the gas on a solid material (such as MOF) facilitates safe, light and economical transport of the gas. This is especially...

    Gaseous energy sources such as hydrogen and natural gas (predominantly methane) encompass an intrinsic transport problem because of their volatility and flammability. Adsorption of the gas on a solid material (such as MOF) facilitates safe, light and economical transport of the gas. This is especially significant in the huge natural gas (NG) market where solutions are required for storage and transport of the gas whether from NG reservoirs in high pressure giant tanks or as a compact low pressure NG tank for small vehicles and other NG powered devices.
    The invention involves a new method for the formation of uniform metal organic frameworks (MOFs) at quantitative yields and in a controlled manner.
    These MOFs can be tailored to adsorb specific gases for low pressure - high volume storage and transport applications.

    Applications


    • Low pressure – high volume gas storage and transportation
    • Safe storage of toxic or otherwise dangerous gases
    • Low energy solid phase gas separation and purification
    • Production of MOF-based catalysts

    Advantages


    • Uniform crystallite morphology
    • A quantitative process
    • Ability to design and control product structure
    • Control of pore size
    • Single step process
    • No additives

    Technology's Essence


    The invention comprises a new solvothermal synthetic procedure in which specific metal ions are selected to react with specific organic ligands to form uniform sub-microstructured MOFs with a narrow size distribution and without the need for a modulator to define the crystal morphology.
    Controlling the selected reagents as well as the specific reaction conditions influences the resulting crystallites formed and enables a fine selection of the desired structure.
    MOFs prepared this way have exceptional uniformity profiles of size and shape and can be tailored to selectively adsorb specific gases for low pressure - high volume storage and transport applications.

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    • Prof. Milko E. Van der Boom
    1782
    L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.Betalains are robust, flavorless, natural water soluble dyes,...

    L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.
    Betalains are robust, flavorless, natural water soluble dyes, in the color ranges of both red-violet and yellow-orange. Currently there is no natural quality source for water soluble natural yellow dyes, with present natural yellow dyes being water insoluble.
    The present technology offers an alternative method that is simple, does not produce side-products, and is non-toxic with Tyrosine being the only feedstock. The technology produces L-DOPA and natural water soluble yellow and red Betalain dyes, both within yeast and in different plant species.

    Applications


    • Production of L-DOPA for use in pharmaceuticals or dietary supplements.
    • Synthesis of water soluble yellow and red natural dyes for use as colorants, antioxidants, and food supplements.
    • Altering coloration of ornamental plants by inserting the metabolic pathway.

    Advantages


    • One-step reaction for L-DOPA synthesis from Tyrosine.
    • Non-toxic and non-hazardous synthesis.
    • Ecologically friendly - no waste management issues.
    • Multiple colors can be produced with yellow, red, or orange if pathways combined.
    • Flavorless - avoid influencing the taste of different products.
    • Flexibility in biosynthetic production - multiple possible host systems.
    • Specificity - no side products produced
    • Mild Conditions - enzyme(s) requires ambient temperatures.

    Technology's Essence


    The present technology takes advantage of the Betalain biosynthetic pathway to selectively produce L-DOPA and natural Betalain dyes. A newly discovered, specific, cytochrome P450-CYP76AD6 begins the pathway, with the capacity to convert Tyrosine to L-DOPA. Then L-DOPA is converted to Betalamic acid via DOPA 4, 5-dioxygenase.
    With the Betalamic acid intermediate, the biosynthetic pathway diverges to make either Betaxanthins (yellow dyes) or Betacyanins (red dyes). In the production of yellow dyes an amine (e.g. amino acid) spontaneously reacts with Betalamic acid. In the case of red dyes, cycloDOPA (generated by the enzyme CYP76AD1 modifying Tyrosine and L-DOPA) and a Betalain-related glucosyltransferase react with Betalamic acid. Furthermore the two pathways can be done in parallel to produce an orange color.

     

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    • Prof. Asaph Aharoni
    1750
    Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases...

    Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.
    Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases, with an exceptionally high potency. Although not as lethal as nerve agents, organophosphate insecticides can be harmful in large or prolonged doses. The standard therapy has limited efficacy, carry risks of serious adverse effects and have relatively short shelf life in field conditions.
    Bioscavengers represent a preferred to rapidly detoxify organophosphates in the blood, before they had the chance to reach its physiological targets and cause damage, but usually require the use of very high doses.
    The present invention provides genetically modified phosphotriesterase (PTE) variants, which serve as catalytic bioscavengers for V-type nerve agents, with exceptional detoxification activity at low doses, and improved stability.

    Applications


    • Prophylactic or post exposure treatment for nerve gases attack, in particular V-type agents
    • Treatment for pesticides poisoning

    Advantages


    • High catalytic activity – allow high efficacy at low doses
    • Reduced effective doses allows to reduce adverse effects
    • High stability increasing shelf life
    • Compatible with both prophylaxis and post exposure
    • Compatible for both surface decontamination and administration to patients

    Technology's Essence


    Researchers at Prof. Tawfik lab use directed evolution to drive protein mutagenesis towards desired traits. Appling this approach, using the actual threat agents, the present inventors generated recombinant phosphotriesterase (PTE) variants with improved catalytic efficiencies towards V-type nerve agent hydrolysis. Serving as catalytic bioscavengers, these recombinant PTE variants hydrolyze organophosphates without being consumed and thus can be applied at low doses (catalytic efficiency (kcat/KM) greater than 3.106 M-1min-1).
    Importantly, PTE is efficient both as a prophylactic agent that may be given several hours prior to exposure as a preventive measure, and as post exposure antidote, even days after in a single or multiple-doses.
    It is compatible with both decontamination of surfaces and detoxification administrated to a patient by standard routes such as orally or injectables.
    Finally, some PTE variants show superior stability properties, retaining at least 50% of their catalytic activity at 50?C, indicating extended shelf life. This may be especially critical in field conditions, where the risk for nerve agent exposure is high.

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    • Prof. Dan S. Tawfik

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