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Technology Name
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Scientist
1665
Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes....

Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.
Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes. Hypertension and diabetes elicit fibrotic processes in the heart, placing a high percentage of the western world population at risk, yet the early identification of fibrotic development in high-risk patients is hindered by lack of adequate fibrosis imaging modalities. This in turn leads to increased morbidity and additional financial burden to health care services. The current standard method to assess myocardial fibrosis employs the usage of MRI coupled with intravenous infusion of Gadolinium contrast agent. However, this method suffers from considerable drawbacks including reduced sensitivity (that permits diagnosis only at advanced stages of disease), lengthy scan times and toxicity of the contrast agent, which excludes a significant subset of patient populations from diagnosis. Thus, the capacity to diagnose myocardial fibrosis in its early stages would allow successful therapeutic intervention, and may also create a platform for the non-invasive study of fibrotic development, thereby facilitating the design of targeted therapies. The current invention is comprised of a novel cardiovascular magnetic resonance method with enhanced sensitivity, without the need for contrast agent administration.

Applications


  • Detection of cardiac fibrosis due to various pathologies, including hypertension, diabetes and heart failure.
  • The method can be applied to detect fibrotic tissues in a broad range of disorders including cancer, renal fibrosis and pathologies related to skeletal muscles.
  • A platform for the clinical study of targeted therapies that may prevent or arrest fibrotic diseases.
  • Monitoring the efficacy of treatment tailored to target fibrotic tissue development.

 


Advantages


  • The method relies on magnetization transfer to provide contrast, and therefore obviates the need for any extrinsic, toxic contrast agent such as Gadolinium.
  • Improved sensitivity over current contrast agent-based cardiac MRI methods.
  • The method can be readily applied to existing MRI clinical imaging systems.

Technology's Essence


A team of researchers at the Weizmann Institute has developed a novel approach for detection of myocardial fibrosis using magnetization transfer contrast (MCT) MRI cardiac imaging technology. The method was tested in vivo on animal models of heart failure and proved highly sensitive for detection of scar tissue formation and monitoring of fibrotic development. One prominent advantage of the present technology over current cardiac imaging modalities is that it eliminates the requirement for extrinsic contrast agents, thereby circumventing potential adverse toxic side effects.

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  • Prof. Michal Neeman
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
1712
  • Prof. Yechiel Shai
1752
Heart failure is the leading cause of death in the western world. Existing treatments fail to compensate the irreversible loss of functional cardiomyocytes (CM), thus presenting a major medical unmet need. Inducing native CM replacement is one approach being tested as regenerative treatment, with the...

Heart failure is the leading cause of death in the western world.
Existing treatments fail to compensate the irreversible loss of functional cardiomyocytes (CM), thus presenting a major medical unmet need. Inducing native CM replacement is one approach being tested as regenerative treatment, with the advantage of a more straightforward methodology over cell transplantation approaches. 
In a multidisciplinary study, headed by Prof. Eldad Tzahor from the Weizmann institute of Science, the tyrosine kinase ERBB2 was shown to be both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
Thus, potentiation of ERBB2 signalling in adult CMs might represent a promising therapeutic approach for CM replacement in heart failure.

Applications


  • Induction of cardiomyocytes replacement therapy following heart injury.

Advantages


  • Straightforward methodology – Avoids complications associated with the requirement for cell transplantation.
  • Include several optional targets - both ERRB2 and its downstream effectors serve as potential targets for therapeutic agents, which may be administrated in combination, to increase chances for successes. 

Technology's Essence


The ligand-receptor network consisting of NRG1, and its tyrosine kinase receptors ERBB4, ERBB3 and ERBB2, plays critical roles during heart development.
In a multidisciplinary study, headed by prof. Eldad Tzahor from the Weizmann institute of Science, ERBB2 was shown to be necessary and limiting for NRG1-induced CM proliferation in the neonate.
Inspired by this finding, the team examined the possibility to use ERBB2 as a target for induced cell proliferation and regeneration in adult hearts. Using loss- and gain-of-function genetic experiments in mice, they reveal that NRG1/ERBB2 signalling is both essential for CM proliferation and heart integrity in the neonatal period, and sufficient to prolong the postnatal proliferative and regenerative windows.
Regeneration was shown to be a result of increased CM dedifferentiation and proliferation accompanied by neovascularization and followed by redifferentiation, tissue replacement with reduced scar formation and restoration of function.
Thus, these finding highlight ERBB2 as a strong target for heart regeneration treatments as well as its downstream effectors.

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  • Prof. Eldad Tzahor
1671
A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined...

A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined conditions required for derivation and long term maintenance of such cells, without genetic modification.
Human naive pluripotent cells can be robustly derived either from already established conventional hESC lines, through iPSC reprogramming of somatic cells, or directly from ICM of human blastocysts. The new human pluripotent state was isolated and characterized; it can open up new avenues for patient specific disease relevant research and the study of early human development.

Applications


  • Reprogramming kits - Somatic cells to iPSC at near 100% efficiency (7days), iPSC to fully naive state.

Advantages


  • Deterministic iPSC reprogramming with no genetic modification required.
  • Stable pluripotency, with low propensity for differentiation
  • Reagents available off-the-shelf.

Technology's Essence


Hallmark features of rodent naive pluripotency include driving Oct4expression by its distal enhancer, retaining a pre-inactivation state of X chromosome in female pluripotent cell lines amongst others. Naive mouse ESCs epigenetically drift towards a primed pluripotent state; while human embryonic stem cells (hESCs) share several molecular features with naive mESCs (e.g. expression of NANOG, PRDM14 and KLF4 naive pluripotency promoting factors), they also share a variety of epigenetic properties with primed murine Epiblast stem cells (mEpiSCs). These observations have raised the question of whether conventioal human ESCs and induced pluripotent stem cells (iPSCs) can be epigenetically reprogrammed into a different pluripotent state, extensively similar with rodent na?ve pluripotency. Researchers at the Weizmann Institute discovered that supplementation of certain chemically defined conditions, synergistically facilitates the isolation and maintenance of pluripotent stem cells that retain growth characteristics, molecular circuits, a chromatin landscape, and signaling pathway dependence that are highly similar to naive mESCs, and drastically distinct from conventional hESCs.

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  • Dr. Jacob (Yaqub) Hanna
1585
Our scientific team has discovered a method to apply the Gabor Transform to signal processing and data compression. Compared to existing methods that are based on Fourier transform, the new method provides for up to 25% savings in content size for video, audio and images, without any loss in quality...

Our scientific team has discovered a method to apply the Gabor Transform to signal processing and data compression.

Compared to existing methods that are based on Fourier transform, the new method provides for up to 25% savings in content size for video, audio and images, without any loss in quality.

By embracing our method, content providers, ISPs and mobile carriers can achieve major savings in data storage and data transfer costs.

Applications


The method can be used in virtually all applications involving data storage, communication and signal processing. One of the main commercial application is for lossy data compression for video, audio and images. Those types of content constitute the bulk of today’s Internet traffic, and improved compression will generate substantial savings in storage and data transfer costs.

The method also applies to the storage, communication and processing of quantum information and may therefore be expected to have applications in quantum calculations, quantum communication and quantum information processing.


Advantages


Existing data compression methods are based on numerical implementations of the Fourier transform, known as FFT, DCT and similar.

Compared to these methods, Gabor transform method demonstrates a very significant advantage in terms of the size of compressed material.  

The method provides for up to 25% savings in data size, while keeping the same perceived quality of the content.


Technology's Essence


We have discovered the definitive solution to the problem of obtaining accuracy and stability in the Gabor transform.  We realized that there must be an exact informational equivalence between the Gabor transform and the discrete Fourier transform (DFT). The latter is known to provide an exact representation of functions that are band-limited with finite support.  Since the DFT implicitly assumes periodic boundary conditions, to obtain this exact equivalence one needs to modify the Gaussians in the Gabor transform to obey periodic boundary conditions. This leads to Gaussian flexibility with Fourier accuracy --- precisely what has been sought since 1946.

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  • Prof. David J. Tannor
1646
Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series...

Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series in one continuous experiment.
In order to design and develop inhibitors for therapeutic purposes, the reaction mechanisms of enzymes must be understood. For biological applications, a common methodology of addressing this need is combining Rapid Freeze Quench with Electron Paramagnetic Resonance (RFQ)-EPR, which allows the trapping and analysis of short lived intermediates in chemical reactions. However, commercial RFQ-EPR devices are limited for high field EPR applications due to the demand of large sample volumes for each time point.
Prof. Goldfarb and her team built a new RFQ apparatus based on microfluidic flow and unique ejection and freezing systems, which can be used for collecting small volume samples in capillaries for high field EPR.

Applications


This technology, combined with the variety of W-band high resolution EPR technique (ENDOR, DEER and ESEEM) enables better mechanistic studies of enzymatic reactions, with an emphasis on structural transformations during the reaction, in an efficient and accurate way.


Advantages


  • Collecting all RFQ time points in one continues experiment.
  • Produce small volume samples in the range of a few µl, and handles small capillaries, for high field ERP.
  • An improved dead time of ~5ms, relative to the commercial RFQs with a typical dead-time of 5–10 ms.
  • Ease-of-use and speed.

Technology's Essence


The innovative apparatus consists of two main parts: the microfluidic device and the freeze-quench setup. The microfluidic device comprises a mixer, which mixes the two reacting solutions, a flow path where the reaction occurs, and a sprinkler from which the solution is sprayed out of the device. Prof. Goldfarb and her colleagues improved the common mixing device by adding a fast stream of nitrogen gas which mixes with the ejected reaction solution, and sprays the frozen aerosol out in tiny drops at high speed.
The innovative RFQ device was planned to have a cold solid surface on which the freezing happens rather than the traditional ejection into a cold liquid, in order to minimize the losses of the frozen solution. Moreover the plate rotates at a speed correlated to the flow speed of the solution, thus samples of different reaction times can freeze on a different radius. The frozen samples are then collected into quartz capillaries.

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  • Prof. Daniella Goldfarb
1555
Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for...

Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for designing an approach to protract the action in vivo of, potentially, any short-lived peptide/protein drug. In doing so two principal obstacles must be overcome: (1) following its conjugation, the probe introduced into a peptide or a protein should have sufficient affinity to albumin to manifest prolonged action in vivo, and (2) in case such covalent introduction results in an inactive product, the latter should be capable to undergo slow reactivation at physiological conditions. The present invention relates to engineering prolonged-acting prodrugs employing an albumin-binding probe that undergoes slow hydrolysis at physiological conditions.

Applications


  • Prolonging half life of short-lined drugs

Advantages


  • Prolonging the action of the drug without effecting its activity 
  • A desirable pharmacokinetic pattern

Technology's Essence


Since albumin is long-lived in vivo, drugs and endogenous substances that tightly associate with it have lower clearance rates than that of the unbound substances, and exhibit prolonged lifetime profiles in vivo. The present invention is based on a concept according to which a long chain fatty acid (LCFA) like albuminbinding compound is covalently linked to a short-lived amino-containing drug to form a non-covalent drug conjugate capable of associating with albumin in vivo, i.e., a long-lived prodrug that gradually releases the pharmacologically active constituent. This approach has been successfully implemented with several drugs (e.g. insulin, exendin and gentamicin).

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  • Prof. Matityahu Fridkin
  • Prof. Yoram Shechter
1616
Existing treatments against cancer are non-sufficiently selective. Immunotherapy based treatment offers highly selective and efficient solution to this problem. A promising approach in Immunotherapy is adoptive cell therapy (ACT). In ACT, therapeutic lymphocytes are administrated to patients in order...

Existing treatments against cancer are non-sufficiently selective. Immunotherapy based treatment offers highly selective and efficient solution to this problem.
A promising approach in Immunotherapy is adoptive cell therapy (ACT). In ACT, therapeutic lymphocytes are administrated to patients in order to treat a disease. In this process antibody-type cells are generated ex vivo, and then infused to the patient. By this technology the cells can be redirected against specific tumors via genetic engineering, using chimeric receptors.
Currently ACT is logistically and economically challenging since it is limited by the used of the patients’ own cells. Another key concern is safety, due to the danger that the allogeneic cells will be rejected by the patient, or will attack the patient.
In cancer, use of tumor specific, chimeric receptor redirected allogeneic T cells can transform ACT into a standardized, off-the shelf therapy. Overall this method proposes a safe and effective adoptive therapy using allogeneic cells while avoiding the use of bone marrow transplantation (BMT).

Applications


  • Cancer immunotherapy

Advantages


  • Off the shelf, standard treatment
  • Safe
  • Effective
  • No bone marrow transplantation (BMT) is required

Technology's Essence


A novel approach for adoptive immunotherapy using fully MHC-mismatch allogeneic T cells. These cells are redirected with tumor specific non-MHC-restricted antibody-based chimeric antigen receptor (T-bodies) in the absence of Graft-versus-host disease (GVHD). In order to create a standardize treatment, the redirection of T cells can be done through an antibody-based chimeric antigen receptor (CAR), thus creating ‘universal effector T cells’. This is based on a combination of of MHC-mismatched allogeneic T-cells with an MHC unrestricted chimeric antigen receptor. These cells would recognize their target independently of MHC restriction, therefore applied as an ‘off-the shelf’ immunotherapy. Regarding the second challenge of avoiding GVHD, by using a controlled lymphodepletion the researchers were able to create therapeutic window during which the allo-T-body cells could destroy the tumor before being themselves rejected.

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  • Prof. Zelig Eshhar
1593
The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders.  To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools...

The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders. 
To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools is to allow individuals identification while maintaining sufficient resolution for accurate tracking.
The present technology provides a system that utilizes fluorescent fur dyes to differentially mark and track individuals within a group. Using a sensitive color camera and a newly designed tracking algorithm, behavior of groups may be recorded and analyzed with high temporal and spatial resolution.   
The technology further offers a method for characterizing the group’s interactions using the maximum entropy model.

 

Applications


 


Advantages


  • High spatial and temporal resolution – enabled by sensitive color video tracking.
  • Enables high detailed analysis of individual behavior within the group.
  • Suitable for community study of groups - limited only by available fur dyes.
  • Compatible with long-term analysis.
  • Simple, cost effective.
  • Minimal suffering and improved animal welfare.

  • Technology's Essence


    The present technology takes advantage of the fact that mice are nocturnal (active at night) animals, to mark their fur with different fluorescent dyes. Under ultraviolet light, the mice can be accurately and automatically tracked, over a number of days. As the mice are allowed to move freely in an interesting arena for exploration containing ramps, nest boxes and barriers (Figure 1), their trajectory and behavior are recorded using a sensitive color camera.
    The system further includes an image processing module which analyses the recorded images, calculates a spatiotemporal model and the nature of social interactions between individuals.
    Combining detailed behavioral and genetic analysis ate the level of individuals, in association with group analysis, may enable the identification of genetic and neuronal correlates of complex social interactions. 

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    • Prof. Alon Chen
    1657
    Bioengineered formatotrophic E.Coli can be utilized to efficiently generate biomass from electricity. A popular direction for cleantech in recent years is that of biorefineries, that use living organisms to supply the human demand for chemical commodities. Electricity is considered to be a potential...

    Bioengineered formatotrophic E.Coli can be utilized to efficiently generate biomass from electricity. A popular direction for cleantech in recent years is that of biorefineries, that use living organisms to supply the human demand for chemical commodities. Electricity is considered to be a potential feedstock for biorefineries, with the end products serving as solid or liquid storage of energy.  Such microbial electrosynthesis is highly dependent on mediators to enable electron transfer from an electrode to a living cell. 
    Formic acid (formate) is an electron mediator with a number of desired features for microbial electrosynthesis. However, wild-type organisms that can grow on formate are not suitable for industrial use due to slow growth rates and metabolism. 
    Researchers at the Weizmann Institute have successfully engineered a formatotrophic E.coli. By combining systematical analysis with computational tools they screened numerous metabolic pathways and identified the optimized metabolic pathway that supports efficient formate-based growth. This innovative method enables the design of industrial strains of bacteria capable of efficient microbial electrosynthesis.

    Applications


    • Biofuel and chemical commodities production.

    Advantages


    • Efficient and robust storage of electrical energy.
    • Cost effective conversion of C1 compounds into sugars.

    Technology's Essence


    By engineering E. coli, the ”workhorse” bacteria used in biotechnology and enabling its growth on formate, researches at Dr. Ron Milo’s lab paved the way for efficient microbial electrosynthesis. The Researches started by investigating many metabolic pathways in order to discover how a model organism such as E.coli can be engineered for formatotrophic growth.  estimate which pathway is most suitable to support growth on formate each pathway was examined based on various criteria such as biomass yield, thermodynamic favorability, chemical motive force, kinetics and additional practical challenges. 
    One short favorable pathway was consistently identified, that is the reductive glycine pathway. Furthermore.  Researches generated an isolated organism that is able to convert formate to pyruvate or glycerate.


    Licensing Status


    Pending

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    • Prof. Ron Milo
    1564
    A new recyclable size-selective filtration device. Particle size, chemical purity and dispersion of nanoparticles crucially determine their optical, electronic and chemical properties. Size-selective separation technologies are becoming increasingly important for the development of nanoparticles with...

    A new recyclable size-selective filtration device.

    Particle size, chemical purity and dispersion of nanoparticles crucially determine their optical, electronic and chemical properties. Size-selective separation technologies are becoming increasingly important for the development of nanoparticles with well-defined sizes, which have application in the fields of optoelectronic devices, biomedicine, materials, and catalysis.

    Researchers at the Weizmann Institute have fabricated supramolecular ultrafiltration membranes that can be used for filtration and size-selective chromatography of nanoparticles. The membranes are composed of a self-assembled three-dimensional fibrous network that is held together by reversible non-covalent interactions.

    The membranes are robust, easy to fabricate, and recyclable.

    Applications


    • Size-selective separation of semiconductor and metal nanoparticles
    • Uniformity and monodispersity of nanoparticles in solution.
    • Size exclusion chromatography of nanoparticles in the sub-5-nm size regime.

    Advantages


    • Efficient and inexpensive

    • Fast and easy fabrication

    • Recyclable

    • Self-assembled

    • Dual application regime: filtration and/or chromatography


    Technology's Essence


    The recyclable supramolecular membranes are formed from unique perylene derivatives that are large and flat aromatic molecules. These molecules are insoluble in water and form a 3-D network over a solid support, which can be used for the separation of nanoparticles.

    The filters can be subsequently recycled from this mixture using an organic solvent (e.g. dichloromethane), which separates the membrane material from the water-soluble nanoparticles, and reused without loss of performance.

    This material is hence highly attractive for application in the field of nanotechnology.

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    • Prof. Boris Rybtchinski
    1628
    New generation of superior nature-inspired therapeutics for treating inflammation.Inflammation is characterized by elevated levels of TNF-?. Neutralizing TNF-? activity was shown to be beneficial for patients with chronic autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and...

    New generation of superior nature-inspired therapeutics for treating inflammation.Inflammation is characterized by elevated levels of TNF-?. Neutralizing TNF-? activity was shown to be beneficial for patients with chronic autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, current treatments of such conditions include general anti-inflammatory and immunosuppressive drugs that are of limited effectiveness and may cause serious side effects. Another class of drugs includes targeted therapies directed against TNF-?, that are associated with serious infections including tuberculosis (TB) and sepsis as well as increased risk of cancer in some cases. Thus, there is an urgent need for highly selective, safer and more effective drugs for inflammatory conditions that involve TNF-? as a key mediator. The present technology introduces a novel generation of candidate drugs that selectively inhibit the processing of TNF-?, thereby preventing it from exerting its pro-inflammatory properties. This technology provides a framework for the development of safer and more effective therapeutics for IBD and related autoimmune disorders.

    Applications


    • Treatment of autoimmune inflammatory conditions such as IBD and RA.
    • Treatment of neuroinflammatory conditions such as multiple sclerosis (MS).
    • Treatment of other inflammatory mediated diseases such as psoriasis, systemic sclerosis and ankylosing spondylitis.
    • All MMPs and ADAMs proteases possess an autoinhibitory pro-domain and therefore this technology can be broadened to other MMP and ADAM targets.

    Advantages


    • TACE pro-domain is highly potent and efficient.
    • TACE pro-domain is metabolically stable, unlike small molecule inhibitors of TACE.
    • Targeting TACE through nature-inspired protein design may constitute a safer approach to combat TNF-? induced inflammation.
    • Unlike non-specific small molecule inhibitors, which target the conserved catalytic zinc site of TACE, TACE pro-domain shares little homology to other MMPs, making it a good candidate for specific inhibitor of TACE.

    Technology's Essence


    The A disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor-? converting enzyme (TACE), has been defined as the major shedding protease for a broad range of substrates predominantly the key immuno-regulatory cytokines TNF-?. Cleavage by TACE renders TNF-? pro-inflammatory, highlighting ADAM17 as a rationale target for treatment of autoimmune diseases such as IBD and arthritis. A team of researchers at the Weizmann institute headed by Prof. Irit Sagi, has employed a sophisticated approach towards TACE targeting by exploiting its autoinhibitory pro-domain as a platform for the ‘smart design’ of TACE selective natural inhibitors. The therapeutic potential of TACE pro-domain was demonstrated in IBD mouse models, where TACE pro-domain administration showed significant improvement in multiple parameters such as reduced mortality and weight lost, in a dose dependent manner. Additional in vivo studies demonstrated that the TACE pro-domain is highly stable in vivo and harbors specificity towards the activated immune cells located in colon lesions. Thus, the novel TACE inhibitor presented in this technology leads to significant therapeutic effects and is beneficial in controlling inflammation in IBD disease manifestations in mice.

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    • Prof. Irit Sagi
    1597
    Metal-oxide material generates electromechanical stress an order of magnitude above existing materials.The ability to develop a mechanical stress in response to the application of an external electric field has many uses, and characteristic materials are classified as either piezoelectric or...

    Metal-oxide material generates electromechanical stress an order of magnitude above existing materials.The ability to develop a mechanical stress in response to the application of an external electric field has many uses, and characteristic materials are classified as either piezoelectric or electrostrictive. Modern inorganic piezoelectric devices are used for a wide variety of applications from inexpensive speakers and headphones, to sophisticated sonar transducers. Over the last several decades, these materials have become highly reliable and technologically mature, but the magnitude of the mechanical stress they can generate in response to an input electric signal has reached an upper limit.This innovative technology applies Gadolinium-doped Cerium Oxide (Gd-doped CeO2) to piezoelectric and electrostrictive devices and will enable high-performance electromechanical materials with output capabilities an order of magnitude above existing solutions, in excess of 500 MPa. This could facilitate the next generation of many consumer and industrial electronic devices.

    Applications


    • Wide range of personal electronic devices
    • Industrial and fine electronics – specifically powerful acoustic transducers

    Advantages


    • Generate large displacement and large stress simultaneously
    • Sensitive and tunable properties

    Technology's Essence


    In piezoelectric devices, stress develops due to the deformation of a non-centrosymmetric lattice under the application of an electric field. In commercial electrostrictors, or materials with centrosymmetric lattices and very large dielectric constants, an external electric field distorts the unit cells of the lattice, rendering them locally non-centrosymmetric. In both cases, the electromechanical stress develops due to a small displacement of atoms within each unit cell. Increasing the magnitude of the response would lead to more powerful actuators, and permit a decrease in the operating voltage; therefore, the search for novel mechanisms of electromechanical response in solids remains an important objective for both fundamental and applied science.

    We have demonstrated that Gd-doped CeO2, specifically Ce0.8Gd0.2O1.9, can generate stress an order of magnitude greater than the best electromechanically active materials. The large stress develops in response to the rearrangement of cerium-oxygen vacancy pairs and their local environment. This effect is expected to be two-fold; i) an applied electric field results in strain and stress directly, and ii) application of the external electric field affects the elastic modulus of Ce0.8Gd0.2O1.9 by suppressing the chemical strain effect. This is a fundamentally different mechanism than materials currently in use. In this view, Gd-doped CeO2 is representative of a new family of high-performance electromechanical materials.

     

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    • Prof. Igor Lubomirsky
    1664
    Neuroinflammation is well established as a key secondary injury mechanism following central nervous system (CNS) trauma, such as brain/spinal injury or ischemic stroke. The neuroinflammation has long been considered to contribute to the damage sustained and fatal outcomes following brain injury....

    Neuroinflammation is well established as a key secondary injury mechanism following central nervous system (CNS) trauma, such as brain/spinal injury or ischemic stroke. The neuroinflammation has long been considered to contribute to the damage sustained and fatal outcomes following brain injury. Alternating between CNS microglia pro and anti-inflammatory activation states is at the core of neuroinflammation initiation and resolution, and failure to switch to the anti-inflammatory state can induce further damage. This can happen under acute or chronic activation as microglia fail to undergo self?resolution of their inflammatory phenotype. Targeting and correcting the balance between microglia activation and suppressive states can therefore reduce brain damage following injury and inflammation.

    The present discovery by the teams of Prof. Michal Schwartz and Prof. Ido Amit elucidates the mechanisms that lead to injury-induced microglia over-activation and proposes IFN-? as a therapeutic strategy to induce microglia to stop their inflammatory response. 

    Applications


    ·           Targeted therapy to reduce neuroinflammation – avoids general immuno-suppressive side effects, treating the cause of inflammation. 

    ·           May allow relatively large therapeutic window – according to proof-of-concept preliminary experiments.


    Advantages


     


    Technology's Essence


    Resident microglia are the major specialized innate immune cells of the CNS. During the process of wound healing or pathogen removal, there is an induction of the microglia active pro-inflammatiry phenotype (M1), leading to a transient inflammatory response, which is resolved via local conversion to the M2 anti-inflammatory phenotype. Following acute injury, microglia fail to acquire M2 phenotype in a timely manner, often resulting in self-perpetuating local inflammation and tissue destruction beyond the primary insult.

    Prof. Schwartz, Prof. Amit, and their respective teams uncovered the mechanisms that lead to injury-based inhibition of the M1 to M2 phenotype switch. They showed that the capacity to undergo pro- to anti-inflammatory (M1-to-M2) phenotype switch is controlled by the transcription factor Interferon regulatory factor-7 (IRF-7). Their results demonstrate that restoring Irf-7 expression by IFN-? (a known IRF-7 activator) reactivates the circuits leading to M2 conversion by improving the resolution of pro?inflammatory cytokines expressed by microglia ex vivo and in vivo, following acute CNS insult.

    Importantly, the anti-inflammatory activity of IFN-? was demonstrated in vivo in mouse models when administrated 24h following the primary insult, proposing a relatively large therapeutic window.

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    • Prof. Michal Eisenbach-Schwartz

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