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Scientist
1795
Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small,...

Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small, difficult-to-reach, spaces for medical and other applications. Multimode fibers are being explored as ultra-thin lensless replacements for the commonly used endoscopes. The difficulty with imaging or focusing light through a multimode fiber is phase randomization of light propagating through the fiber, which results in a complex speckle pattern at the fiber output. To overcome this obstacle, an access to both fiber ends is required for pre-calibration.

A novel endoscopic method that was developed by Prof. Silberberg at the Weizmann Institute of Science allows light focusing through a multimode fiber by approaching solely the proximal end and retrieving information about the distal end using non-linear optical feedback.

Applications


·         Clinical imaging of narrow cavities (blood vessels, respiratory system, joints, etc.)

·         Selective targeting and burning of fluorescent targets (imaging and treatment)  


Advantages


  • Ultra-thin (micro-meter scale) and flexible

  • Lensless endoscopy

  • High resolution and accuracy


Technology's Essence


We consider a two-photon lensless multimode fiber-based endoscope, where an ultrashort pulse is delivered to a fluorescently tagged sample through the fiber. The pulses excite two photon fluorescence (2PF) from a 2PF screen placed against the fiber distal end. The back-propagated 2PF that is collected by the same fiber is separated from the excitation light at the proximal end by a dichroic mirror (DM), and the Fourier-transformed image of the fiber facet is recorded by an EMCCD camera. It is then used as feedback for a wavefront-shaping optimization algorithm, controlling a spatial light modulator (SLM) at the proximal fiber end. The nature of the light propagation in the fiber allows for scanning and controlling the focus position at the fiber distal end.

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  • Prof. Yaron Silberberg
1798
The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as...

The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as cosmetics, paints and jewelry due to its pearlescence effect. However, the industrial application of guanine crystals is limited since they are extracted from biological sources (mostly fish scales) with limited control over crystals dimensions, morphology and quantity for industrial applications. The main reasons impeding the use of synthetic guanine crystals are guanine insolubility in most solvents and the difficulty of obtaining crystals in the desired morphology. For these reasons, there is a thriving need for the development of a synthetic approach for the formation of well-defined anhydrous guanine crystals with tailor-made properties.

The new technology provides a novel synthetic method for the preparation of highly versatile pearlescent materials, based on guanine crystals, from aqueous solutions. The controllable size and shape of the resulting materials and the sustainability of the method make them suitable alternatives for the existing naturally occurring pearlescent pigments.

Applications


·      Cost-effective and environmentally-friendly approach

·      Control over crystals properties, including size and phase (anhydrous guanine and guanine monohydrate)

·      The same technology can be applied for the crystallization of other materials (purines and pteridines)


Advantages


·      Cosmetics and personal care products

·      Printing inks and decorative paints

·      Automotive paints.


Technology's Essence


Guanine is practically insoluble in neutral aqueous solutions. However, in aqueous acidic or basic solutions, where the molecules are ionized, guanine is much more soluble. The process involves dissolving guanine powder in either acidic or basic solutions, using HCl or NaOH, respectively, and then inducing crystallization by adjusting the pH of the solution. The crystal morphologies differ significantly when carrying out the crystallization in solutions adjusted to different pH regimes. Using pH induced crystallization, the interplay between the initial guanine concentration and the rate of pH change allow substantial control over the crystallization process and ultimately over the crystal size.

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  • Prof. Lia Addadi
1801
A new image processing tool for transient detection was developed by the group of Prof. Gal-Yam, originally for time-domain observational astronomy.Image sequences are used in various fields, including medical imaging and satellite/airborne imaging. The comparison between images taken at different...

A new image processing tool for transient detection was developed by the group of Prof. Gal-Yam, originally for time-domain observational astronomy.
Image sequences are used in various fields, including medical imaging and satellite/airborne imaging. The comparison between images taken at different conditions (e.g. equipment or configuration, angles, weather and wavelength) can be a highly non-trivial problem, as subtraction artifacts can outnumber real changes between images.
The existing remedy for this problem includes highly complex solutions using machine learning algorithms to narrow the sea of candidates. In some cases, human interpretation of images cannot be avoided, resulting is very long processing times.
The new method presented here provides a proven solution for the subtraction of images taken at varying conditions. The tool can be applied for any type of imaging, allowing fast processing and accurate results.

Applications


  • Satellite/airborne imaging

  • Medical imaging
  • Defect detection

Advantages


  • Fast and automatic

  • Generic, can be applied to various imaging scenarios
  • Easily implementable into existing systems

Technology's Essence


The new method is used for processing at least two N-dimensional data-measurements (DMs) of a physical-property for detecting one or more new-objects and/or a transition of one or more known-objects, in complex constant-background DMs. Generally, the

the method includes: (1) generating a filtered-new-DM by match-filtering a new-DM, respective to impulse response of a reference-DM (2) generating a filtered-reference-DM by match-filtering the reference-DM, respective to impulse response of the new-DM (3) generating an N-dimensional object-indicator (OI) by subtracting the filtered-reference-DM from the filtered-new-DM, or vice versa and (4) generating an N-dimensional data score from the N-dimensional OI, where each of the scores is a probe for existence of an object at a specific N-dimensional location.
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  • Prof. Avishay Gal-Yam
1690
Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause...

Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause of slow or incomplete fermentation and product downgrading. Standard anti-phage measures (sanitation, culture handling) fail to provide sufficient protection, exposing the production process to massive economic setbacks.
Extensive R&D efforts have led to the discovery of phage resistance systems, however many phages can circumvent these systems, and in addition not all LABs can accommodate them.
Therefore, there is a strong need for additional defense systems that could naturally protect LABs against phages.
The Sorek laboratory at the Weizmann Institute of Science has recently identified hundreds of novel functional toxin/antitoxin systems in bacterial genomes. These systems were discovered using analysis of data from millions of shotgun cloning experiments across 388 bacterial species. Acting as an abortive infection agent to prevent phage spread, some of these systems were already validated as conferring resistance against phage infection upon introduction to E.coli cells.
In another novel technology, researchers at Dr. Rotem Sorek’s lab identified a novel anti phage gene cassette, termed BREX (Bacteriophage Exclusion), which confers complete or partial resistance against phages spanning a wide phylogeny of phage types, including lytic and temperate ones.

Applications


  • Tools for conferring anti-phage traits to bacterial starters.

Advantages


  • Provides efficient phage-resistance features.
  • Robust: confers resistance to a broad range of phages, including both lytic and temperate ones.
  • General: the same defense system may be applied in various cultures, not confined to specific strains.
  • Novel systems, provides a fresh approach to the field of phage resistance 

Technology's Essence


Toxin/antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, are proposed to function in phage defense via abortive infection. The two genes, which reside on the same operon, code for small proteins where inhibition of the toxin is carried out through protein-protein interaction. Upon a specific signal (phage infection) the antitoxin degrades rapidly by one of the housekeeping bacterial proteases, resulting in either bacteriocidic (cell-killing) or bacteriostatic (growth-inhibiting) effects, thus protecting the colony against phage spread. The inventors took advantage of the concept that toxins could only be cloned when the neighboring antitoxin was present on the same clone to systematically reveal active TA pairs. Following extensive statistical and experimental validations, 8 novel families of TA pairs that are likely to play a role in phage defense were identified. By introducing these systems into new bacteria, the inventors showed that the toxin/antitoxin pairs could protect the engineered bacteria from phage infection.
BREX is a novel cassette of six genes that confers protection against a wide range of phages, including virulent and temperate ones. This cassette is composed of genes not typically found in other defense systems, and hence employs a novel mechanism of anti-phage protection. Scientists at the Sorek lab further uncovered the mode of action of this novel system. It was shown that the system is not an abortive infection system (i.e., does not lead to suicide of the infected cell), and that it allows phage adsorption but blocks phage replication in a DNA degradation independent manner.

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  • Prof. Rotem Sorek
1730
Production of carbon nanotube based transistors through a process comprised of identification, selection, and placement of pristine carbon nanotubes in conjunction with standard electrical circuitry.Semiconductor devices are vital to everyday life, however conventional semiconducting materials are...

Production of carbon nanotube based transistors through a process comprised of identification, selection, and placement of pristine carbon nanotubes in conjunction with standard electrical circuitry.
Semiconductor devices are vital to everyday life, however conventional semiconducting materials are quickly approaching their limitations. As devices transition from the microscale to the nanoscale, new techniques for their assembly and testing of their properties must be created. Controllable nanofabrication methods are of increasing importance across a wide field of electronics in everything from energy efficient LEDs in flat-screen monitors to transistors for ultra-powerful computers. Our process presents a novel method for producing high quality nanoscale carbon nanotube based transistors. These methods will be of the utmost importance in the forthcoming nano-revolution.

Applications


  • Produce flawless carbon nanotubes
  • Identify, select, and position nanotubes with precision
  • Room temperature operation
  • High sensitivity
  • High resolution

Advantages


  • Single electron transistor (SET) nanoscale imaging
  • Novel nano-electromechanical devices

Technology's Essence


The principle behind this technology is two-fold: 1) Synthesis and selection method of flawless carbon nanotubes, and 2) their combination with nanoscale electric circuitry to form fully controlled composite nanoscale electronic device.
Selection of the carbon nanotube(s) is assisted by a scanning probe microscope (SPM). A composite electronic device is assembled from two separated chips; a nanotube chip where nanotubes are grown over wide trenches, and a standard circuit chip with electrode contacts surrounding the gates to be measured. The nano-assembly is achieved by inserting an SPM cantilever into a trench on the nanotube chip and placing the circuit chip over a suitable nanotube. Once in place, the nanotube is cut locally by passing a strong current between the electrode contacts, and the composite chip is formed.
This composite electronic device can be used to map electronic potentials with high resolution of 100 nm, high sensitivity of 1microV/Hz1/2, at frequencies of 100 MHz and more and all this at room temperature.

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  • Prof. Shahal Ilani
1758
For patients with AML, identification of their specific subtype and genetic background is crucial for predicting their outlook and decision of treatment. Therefore, understanding the molecular characteristics of specific subtypes of AML can lead to novel therapeutics and improve patient survival.   The...

For patients with AML, identification of their specific subtype and genetic background is crucial for predicting their outlook and decision of treatment. Therefore, understanding the molecular characteristics of specific subtypes of AML can lead to novel therapeutics and improve patient survival.  
The present invention relates to a unique vulnerability of AML subtypes, in which specific chromosome abnormalities result in the dependence of the cancer cells on the activity of native RUNX1. Selective inhibition of RUNX1 under these genetic backgrounds results in killing of the cancer cells.  Thus, the methods described in this innovation may lead to the development of novel AML therapeutics.

Applications


 


Advantages


  • Specificity – targets a signaling vulnerability which is unique to AML and does not occur in healthy cells.
  • Critical impact – the inhibition of RUNX1 in addicted cells induces irreversible killing of the cancer cells by apoptosis rather than just inhibiting their proliferation.
  • Targeting RUNX1 in the addicted AML subtypes can potentially improve patient survival and also be used as a therapy for patients which developed secondary resistance in response to conventional chemotherapy.   

Technology's Essence


The RUNX1 transcription factor is a frequent target of various chromosomal translocations.
The t(8;21) and inv(16) AML subtypes create oncoproteins which interfere with RUNX1 activity in a dominant-negative manner.
While RUNX1 is frequently inactivated in other forms of AML, an active RUNX1 allele is maintained in both t(8;21) and inv(16) AML patients, underscoring the medical significance of native RUNX1 in A-E and C-S mediated leukemogenesis.
Knockdown (KD) of RUNX1 in cell culture models for A-E and C-S showed that these cells are physiologically dependent on RUNX1 activity for their survival and inhibition of RUNX1 in these cells leads to apoptotic cell death. This apoptosis is triggered by decreased expression of key mitosis-regulatory gene.
Therefore, AML subtypes associated with an altered RUNX1 activity or expression are addicted to native RUNX1 for their survival.  Targeting RUNX1 in these patients is expected to activate apoptosis and compromise leukemogenesis.
Thus, the genetic addiction described in the current innovation can be used for the development of novel targeted therapies for AML.

 

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  • Prof. Yoram Groner
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
1696
A new method for observing large areas with physically small detectors, which are unable to cover the whole area simultaneously, based on multiplexing several scanned areas onto a single detector unit followed by algorithmic reconstruction of the true field of view. Astronomical observations require...

A new method for observing large areas with physically small detectors, which are unable to cover the whole area simultaneously, based on multiplexing several scanned areas onto a single detector unit followed by algorithmic reconstruction of the true field of view.
Astronomical observations require the ability to detect very weak signals at high spatial resolution. This reflects on the special characteristics of the observation systems; they need to have a large aperture, high resolution detectors and very low system noise. These demands render high costs and complexity.
Our multiplexing and reconstructing method was developed based on the sparse nature of astronomical observations, and it could be implemented in any application in which sporadic data points are to be found against a fixed (whether detailed or blank) background.

Applications


  • Highly efficient telescopes
  • Quick quality assurance systems – fault metrology
  • Implementation in microscopy

Advantages


  • Use of small size detectors
  • Ability to scan large fields (compared to detector size)
  • Maintaining high resolution
  • Significant shortening of scan time
  • Easily applicable to existing systems

Technology's Essence


The method was developed for astronomical observations in which the studied field is immense and the detector size is relatively small and limited. The invention consists of an optical system that directs light (IR, Vis, UV or other) from different locations in the sky to the focal plane of a telescope onto a specific single detector area, creating a multiplexed image in which several portions of the sky are presented collectively.
Such multiplexing is done on each detector unit area with a different set of sky loci.
A reconstruction algorithm was developed to construct sub-observations sets in a method that guarantees unique recovery of the original wide-field image even when objects overlap.

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  • Prof. Avishay Gal-Yam
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
    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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    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
    1710
    Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways...

    Dysregulation of the immune system is the underlying cause of potentially fatal conditions such as sepsis and severe allergic reactions. Adequate therapies are currently absent or lacking. There is therefore an unmet medical need for therapies that would target the underlying causative immune pathways.
    Anti-microbial peptides (AMPs) possess promising anti-inflammatory activities, however, are commonly toxic.
    In a series of newly synthesized peptides, the outlined invention provides a method to modify naturally occurring AMPs to possess both potent therapeutic anti-inflammatory activity and minimal toxicity in-vitro and in-vivo.
    The resulting series of peptides were shown to remarkably inhibit severe allergic reaction as well.

    Applications


    • Novel Therapy for sepsis and severe allergic reactions

    Advantages


    • Very potent anti-inflammatory and anti-allergenic agents
    • Non-toxic
    • Targeted against the underlying cause of both indications, which is an improper and uncontrolled immune response
    • Diversity – elucidating the parameters that control efficiency and toxicity allows to modify the basic formula to optimally fit different systems

    Technology's Essence


    With natural AMPs properties in mind, Prof. Shai and his team characterized the key modifications that underline anti-inflammatory activity and toxicity. A series of peptides with variable degrees of hydrophobicity, length, charge, position of charge and amino acid chirality were tested for their LPS neutralizing activity.
    It was found that ~20mer peptides under the formula Kn(AL)mKn (wherein n et each occurrence is independently 0-2, and m is 6-9) demonstrate anti-inflammatory activities at nanomolar concentrations as evident by inhibition of TNF? secretion from macrophages, following  LPS induction. Furthermore, a single dose of an exemplary peptide was able to inhibit septic shock in mice induced by purified LPS or by whole heat-killed E.coli.
    In contrast to previous attempts, which focused on increasing hydrophobicity, the core of the present invention is the designation of an optimal hydrophobicity that is necessary for high activity and low toxicity. Additional important features for LPS neutralizing were found to be ?-helical structure and strong oligomerization ability.
    Surprisingly, the present peptides were shown to contain highly potent anti-allergenic activity as well. In-vitro inhibition of Fc?RI-mediated degranulation was recapitulated in-vivo  

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    • Prof. Zelig Eshhar
    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
    1679
    A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combinationBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect...

    A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combination
    Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect women at a younger age. Unfortunately TNBC cannot be treated with the common receptor targeted therapies since it does not express these targets, the estrogen, progesterone and Her2/neu receptors. Therefor systemic treatment options are currently limited to cytotoxic chemotherapy. The lack of effective targeted therapies, resistance to chemotherapy, and early metastatic spread have contributed to the poor prognoses and outcomes associated with TNBC.
    The current technology offers a novel therapeutic strategy for TNBC. The application of two novel, noncompetitive antibodies against EGFR, achieves a robust degradation EGFR resulting in tumor inhibition.

    Applications


    • Novel and unique antibody targeted therapy for TNBC.
    • The novel anti EGFR antibodies can cooperate synergistically with the currently marketed EGFR antibodies.

    Advantages


    • A promising therapeutic scenario to treat TNBC.
    • Enhanced EGFR degradation and improved anti-tumor activity, in contrast to clinically approved anti-EGFR mAbs, which display no cooperative effects.
    • Lysosomal EGFR degradation pathway induced by epitope-distinct antibody mixture may potentially lead to improved therapeutic outcome, and reduced resistance.

    Technology's Essence


    Prof. Yosef Yarden and his team demonstrated that a combination of novel antibodies that target distinct regions on the human EGF receptor resulted in its robust and synergistic down-regulation, leading to pronounced tumor growth inhibition. Furthermore, the combined mAbs induced lysosomal degradation of EGFR, while avoiding the recycling route. Such irreversible mode of EGFR degradation may potentially increase response rate or delay the onset of patient resistance.
    Conversely, combining cetuximab and panitumumab, the mAbs routinely used to treat colorectal cancer patients, did not improve receptor degradation because they are both attracted to the same epitope on EGFR.

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    • Prof. Yosef Yarden
    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

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