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Technology Name
Briefcase
Scientist
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
1629
A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.Nearly...

A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.
Nearly all methods analyze pathway activity in a global “atomistic” manner, based on an entire sample set, not attempting to characterize individual tumors. Other methods use detailed pathway activity mechanism information and other data that is unavailable in a vast majority of cancer datasets.
The new algorithm described here transforms gene-level information into pathway- level information, generating a compact and biologically relevant representation of each sample. This can be used as an effective prognostic and predictive tool that helps healthcare providers to find optimal treatment strategies for cancer patients. Furthermore, this method can be generically used for reducing the degrees of freedom in order to derive meaningful output from multi-dimensional data using limited knowns.

Applications


  • Personalized cancer treatment.
  • A tool for mining insight from large datasets with limited knowns.

Advantages


  • Provides personalized solutions.
  • Can be utilized for rare conditions with very limited known information.
  • Proved on real oncologic datasets.
  • A Generic unsupervised learning tool.

Technology's Essence


The algorithm analyzes NP pathways, one at a time, assigning a score DP(i) to each sample i and pathway P, which estimates the extent to which the behavior of pathway P deviates from normal, in sample i. To determine this pathway deregulation score the expression levels of those dP genes that belong to P using available databases are used. Each sample i is a point in this dP dimensional space; the entire set of samples forms a cloud of points, and the “principal curve” that captures the variation of this cloud is calculated. Then each sample is projected onto this curve. The pathway deregulation score is defined as the distance DP(i), measured along the curve, of the projection of sample i, from the projection of the normal samples.

 

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  • Prof. Eytan Domany
  • Prof. Eytan Domany
1633
The ErbB family consists of four structurally related receptor tyrosine kinases. Excessive ErbB signaling is associated with enhanced tumorogenesis, and as such serves as a major therapeutic target in a wide array of solid tumor cancers. A member of this family, the human epidermal growth factor...

The ErbB family consists of four structurally related receptor tyrosine kinases. Excessive ErbB signaling is associated with enhanced tumorogenesis, and as such serves as a major therapeutic target in a wide array of solid tumor cancers. A member of this family, the human epidermal growth factor receptor 2 (ErbB-2/HER2), is overexpressed in a variety of human cancers, including breast and gastric tumors. ErbB-2/HER2 amplification correlates with elevated metastatic activity and poor prognosis. An innovative and highly potent approach for cancer treatment is proposed here, based on delivering novel nucleic acid-based entities called aptamers targeting ErbB-2/HER2. Remarkably, the antitumor effect exerted by the multimeric anti-ErbB-2/HER2 aptamers is twofold stronger than that elicited by currently available antiErbB-2 monocolonal antibodies.

Applications


  • A novel class of molecules for the treatment of human cancers exhibiting excessive ErbB-2/HER2 signaling.
  • Combination with other therapeutic modalities may predictably enhance the antitumor activity of the aptamer.
  • Aptamers may also be harnessed as carrier molecules to deliver toxic loads into cancer cells.

Advantages


  • Unlike traditional methods for producing monoclonal antibodies, no organisms are required for the in vitro selection of oligonucleotides. This facilitates the selection and chemical design process of aptamers.
  • Aptamers are produced chemically in a readily scalable process.
  • Non-immunogenic.
  • Unlike other oligonucleotide-based therapeutics (siRNAs, antisense RNA), aptamer therapeutics can be developed for intracellular as well as extracellular or cell-surface targets.

Technology's Essence


Aptamers are single-stranded oligonucleotides that fold into defined architectures and avidly bind to targets such as proteins, with the same effectiveness and affinity associated with mAbs. Using a novel screening technology the research team has identified a multimeric aptamer with pronounced ErbB-2/HER2 inhibitory activity. Preliminary preclinical experiments show that treatment of gastric tumor-bearing mice with trimeric aptamer resulted in reduced tumor growth that was nearly twofold stronger than that achieved with a monoclonal anti-ErbB-2/HER2 antibody.

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  • Prof. Yosef Yarden
  • Prof. Michael Sela
1640
Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The...

Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The present invention provides highly selective targeted therapy against MMP-7, which is strongly associated with aspects of cancer development such as angiogenesis and metastasis.
The innovative concept leading to this high selectivity is immunization with both a synthetic metal-protein mimicry molecule, previously developed by the present inventors, followed by the metalloenzyme itself (e.g. MMP-7). The resulting antibody exhibits exceptional degree of specificity towards MMP-7 over other MMPs.
The present technology offers an opportunity to re-introduce improved MMP-targeting agents to the cancer therapeutics market, in particular aggressive cancers that face a major unmet medical need. 

Applications


  • Therapy for MMP-7 associated diseases
  • Diagnostic tool for MMP-7 associated diseases

Advantages


  • Highly selective
  • Safe – avoids adverse effects that are associated with broad spectrum MMP inhibitors.
  • Efficient – targeting a physiological active conformation of the enzyme

Technology's Essence


The present technology is based on a previous invention that was developed in Prof. Sagi's lab, of synthetic metal-protein mimicry molecules that mimic the conserved structure of the metalloenzyme catalytic zinc-histidine complex within the active site of each MMP enzyme.
These molecules were shown to be powerful immunogens in the generation of highly selective MMP antibodies since they recognize both electrical and structural determinants residing within the enzyme active site. The potential of this method to successfully generate MMP-targeting therapeutics was shown for MMP-9/2 inhibitory antibodies in mouse models of inflammatory bowel disease.
Prof Sagi and her team now take this invention a step further to achieve even higher specificity. They show that immunizing with the mimicking molecules described above, followed by immunization with the metalloenzyme itself increases selectivity further.   
Implemented for MMP-7-targeting, this approach yielded an antibody with a 5 fold lower Ki towards MMP-7 than towards other MMPs (e.g. MMp-2 and MMP-9).


 

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  • Prof. Irit Sagi
  • Prof. Irit Sagi
1642
A potential target for anticancer drug design.Cancer is the second leading cause of death in the US, accounting for roughly 23% of all deaths (as of 2008), and with estimated cost of care of $157 billion (as of 2010). Despite major advances in the management of cancer, most types of solid tumors remain...

A potential target for anticancer drug design.
Cancer is the second leading cause of death in the US, accounting for roughly 23% of all deaths (as of 2008), and with estimated cost of care of $157 billion (as of 2010). Despite major advances in the management of cancer, most types of solid tumors remain resistant to conventional treatment modalities. The local microenvironment, or niche, of a cancer cell plays important roles in cancer development. A major component of the niche is the extracellular matrix (ECM), a rich mesh of fibrous proteins surrounding cells that has been shown to exert a protective and supporting effect on cancer progression. Therefore, targeting the ECM represents a novel avenue for rational anticancer drug design. The current technology allows for specific targeting of an enzyme that takes part in ECM assembly and maintenance, and may provide a novel means for combating cancer progression and metastasis emergence.

Applications


  • Inhibitory antibodies to block QSOX1 catalytic activity in ECM as means to combat cancer progression and metastatic disease.
  • ]QSOX1 inhibition may also be utilized to treat lamin-associated disease.

Advantages


  • Since QSOX1 functions outside cells it would be accessible to antibodies that are not readily taken up by cells.
  • Since the microenvironment confers anticancer therapy resistance, a treatment that specifically targets the stromal cells may be synergistically combined with existing therapeutic modalities.

Technology's Essence


A team of researchers at the Weizmann Institute have that a secreted disulfide bond catalyst known as Quiescin sulfhydryl oxidase 1 (QSOX1) is required for proper assembly of the ECM. The main substrates of QSOX1 within the ECM are laminins. Thus, cells lacking QSOX1 show poor incorporation of laminin into the ECM mesh, resulting in decreased cell adherence and perturbed cell migration. Notably, in some cancer types such as pancreatic and breast cancers, QSOX1 and the ECM components it produces are over-expressed. This suggests that modulation of QSOX1 activity may provide a novel means to combating cancer and metastasis. Treatment of cancer cells with a monoclonal QSOX1-targeting antibody effectively blocked cell migration and provides a novel strategy for cancer treatment by QSOX1 inhibition.

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  • Prof. Deborah Fass
1644
Computer memory and storage are among the most critical components of today’s consumer electronics and computer technology. Currently available memory and storage technologies have inherent limitations that confine the capacity and speed of access to memory devices. The present innovation is based on...

Computer memory and storage are among the most critical components of today’s consumer electronics and computer technology. Currently available memory and storage technologies have inherent limitations that confine the capacity and speed of access to memory devices.

The present innovation is based on Chiral Induced Spin Selectivity (CISS) effect that was established experimentally and theoretically in the last decade, and allows for production of inexpensive, high-density universal memory-on-chip devices, that don’t require the use of permanent magnets.

Applications


·         Inexpensive, high-density universal memory-on-chip devices

·         The technology can be used as superior alternative for both Random Access memory and Flash memory

·         Surface-controlled spintronic devices

·         Logic and data processing


Advantages


·         Up to 70 times more storage on the same physical size

·         Up to 100 times lower energy consumption

·         Si-Compatible

·         High density (can reach Si technology limit)

·         Estimated low cost

·         Overcomes limitations of other magnetic-based memory technologies


Technology's Essence


Ferromagnets can be magnetized either by external magnetic fields or by spin polarized current. However, the current density required for inducing magnetization is extremely high and significantly affects the device’s structure and performance. The newly discovered CISS effect allows for magnetization switching of Ferromagnets, which is induced solely by adsorption of chiral molecules, where much lower current density is sufficient to induce the magnetization reversal. Chiral Memory technology uses the CISS effect for spin selectivity instead of the common ferromagnetic-based spin filters. This allows, in principle, the memory bit to be miniaturized down to a single magnetic nanoparticle or a nano-scale domain. The operation principle of the device relies on the spin-selective transmission of electrons through organic chiral molecules to the ferromagnetic layer of the device, which results in the magnetization of this layer and efficient storing of bits of information. The magnetization switching by local adsorption of chiral molecules eliminates the need for a permanent magnet.

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  • Prof. Ron Naaman
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
1647
Novel algorithms developed at the Weizmann Institute of Science for Content-Based Image Retrieval (CBIR) can enhance search engines by crowd-sourcing and improved clustering.Discovering visual categories among collection of images is a long standing challenge in computer vision, which limits images-...

Novel algorithms developed at the Weizmann Institute of Science for Content-Based Image Retrieval (CBIR) can enhance search engines by crowd-sourcing and improved clustering.
Discovering visual categories among collection of images is a long standing challenge in computer vision, which limits images-based search engines. Existing approaches are searching for a common cluster model. They are focused on identifying shared visual properties (such as a shared object) and subsequently grouping the images into meaningful clusters based upon these shared properties. Such methods are likely to fail once encountering a highly variable set of images or a fairly limited number of images per category.
Researchers form Prof. Michal Irani lab suggest a novel approach based on ‘similarity by composition’. This technology detects statistically significant regions which co-occur across images, which reveals strong and meaningful affinities, even if they appear only in few images. The outcome is a reliable cluster in which each image has high affinity to many images in the cluster, and weak affinity to images outside the cluster.

Applications


  • Images search engines - can be applied for collaborative search between users.
  • Detecting abnormalities in medical imaging.
  • Quality assurance in the fields of agriculture, food, pharmaceutical industry etc.
  • Security industry- from counting people up to identifying suspicious acts.
  • Computer games and brain machine interface.

Advantages


• Can be applied to very few images, as well as benchmark datasets, and yields state-of-the-art results.
• Handles large diversity in appearance.
• The search is not a global search, it requires no semantic query, tagging or pre-existing knowledge.
• The multi-images collaboration significantly speeds up the process, reducing the number of random samples and iterations.
• Set of images are obtained in time which is nearly linear in the size of the image collection.


Technology's Essence


In “clustering by composition”, a good cluster is referred as one in which each image can be easily composed using statistically significant pieces from other images in the cluster while is difficult to compose from images outside the cluster. Multiple images exploit their ‘wisdom of crowds’ to further improve the process. Using a collaborative randomized search algorithm images can be composed from each other simultaneously and efficiently. This enables each image to direct the other images where to search for similar regions within the image collection. The resulted sets of images affinities are sparse yet meaningful and reliable.

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  • Prof. Michal Irani
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
1658
Rapid, label free assay for glycan identification, accessible for use in medical diagnostics and biomanufacturing quality control. While glycans hold great promise as biomarkers for several diseases including cancer, technologies that enable rapid and sensitive glycan analysis for diagnosis at “point...

Rapid, label free assay for glycan identification, accessible for use in medical diagnostics and biomanufacturing quality control.

While glycans hold great promise as biomarkers for several diseases including cancer, technologies that enable rapid and sensitive glycan analysis for diagnosis at “point of care” settings are not available.

Dr. Margulies and his team from the Weizmann institute of science developed an optical biosensor that is based on combinatorial detection and produces distinct optical “signatures” for even closely related glycan species.

This invention may be implemented into a single device, which will be simple to operate, to identify many types of glycans in high sensitivity for clinical diagnosis and biomanufacturing quality control processes.

Applications


  • Point of care biosensor device for routine detection of glycan biomarkers from clinical samples.

  • Quality control biosensor device for glycans biomanufacturing.


Advantages


  • Label free, rapid, and easy to integrate into a compact self-contained "point of care" system.

  • Highly sensitive due to the combinatorial effect.

  • A single compound identifies many analytes.

  • Ease of miniaturization for future applications.


Technology's Essence


The present invention is based on a multi-sensor array compound which is composed of a non specific receptor (e.g. boronic acid), at least three chromophores and an anchor. The binding event of this compound to an analyte (i.e. carbohydrates, saccharides) is transduced into a measurable optical signature.

The binding of different analytes distinctly affects the emission of each dye, due to direct optical responses of each dye, as well as conformational changes that affect fluorescence resonance energy transfer (FRET) processes among them. Other photochemical processes that further contribute to the discrimination ability of this innovative compound are photo-induced electron transfer (PET) and internal charge transfer (ICT).

The combination of these effects provides a vast number of unique optical signatures. The pattern recognizer evaluates the responses and through predetermined, programmed, or learned patterns, compares the unique pattern or signature of the measurements to stored patterns for known biomarker or chemical species.

Finally, this design is extremely simple to operate and utilizes a single instrumentation, a single excitation wavelength, and a single incubation step, all of which enable straightforward analysis.

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  • Prof. David Margulies
1662
Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and...

Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and cancerous cells. Also, the therapeutic role of the immune system is an essential element in the healing process due to bone marrow transplantation for hematologic malignancies.
However, a more efficacious and less toxic T cells based treatment is required. Effective therapy depends on the functional avidity between T cell receptors (TCRs) and peptide-MHC complex (pMHC). However the natural affinity of TCR is low and they do not naturally undergo the processes that improve antibody affinity, such as somatic hypermutation (SHM). Currently there is no method of increasing the affinity of a TCR to its ligand. Moreover there is no knowledge on how use affinity maturated TCRs for creating anti-tumor reactive cells
This technology presents a method of increasing the affinity of a TCR to its ligand. This is done by subjecting TCR genes to SHM via the enzyme Activation Induced cytidine Deaminase (AID). The technology further provides affinity maturated TCRs (in cell- bound or in soluble form) and their pharmaceutical potential for immunotherapy. 

Applications


  • Generating anti-tumor T cells
  • Generating T cells reactive against selected antigen

Advantages


  • Rapid
  • Effective

Technology's Essence


This novel technology reveals that the affinity of a TCR to its ligand may be increased remarkably by subjecting TCR genes to SHM, directed by AID.
First a nucleic acid construct encoding a TCR gene is expressed in a host cell. Next SHM is used to introduce mutations to the TCR gene. Last, the the cells will be analyzed for affinity maturation by tetramer staining and subsequently sorted by FACS.
There are three parallel approaches to perform affinity maturation for the TCR: (1) Ex-vivo affinity maturation system, using Tet-regulated expression of AID (2) Ex-vivo affinity maturation system, using controlled expression of AID by mRNA electrophoresis (3) In-vitro affinity maturation system, using extracts from cells that are in SHM and recombinant AID.

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  • Prof. Rachel Lea Eisenbach
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
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
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
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

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