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

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

Applications


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

Advantages


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

Technology's Essence


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

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  • Prof. Dan S. Tawfik
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
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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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
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
1601
A potent combination therapy against non-invasive breast cancer Breast cancer is the most common cancer in females. Among the different subtypes of breast cancer, ductal carcinoma in situ (DCIS) represents an intermediate step between normal breast tissue and invasive breast cancer. Currently, about 25...

A potent combination therapy against non-invasive breast cancer

Breast cancer is the most common cancer in females. Among the different subtypes of breast cancer, ductal carcinoma in situ (DCIS) represents an intermediate step between normal breast tissue and invasive breast cancer. Currently, about 25% of breast cancers that are diagnosed in the US are DCIS. DCIS is commonly treated by surgical intervention followed by adjuvant radiation therapy. However, a significant fraction of the DCIS lesions, which display HER2 gene amplification, are associated with increased relapse rate following surgery. Therefore, in cases of HER2-overexpressing DCIS a molecularly targeted therapy might be necessary for complete eradication of microscopic remnants following surgical tumor removal. The current technology presents an potential DCIS therapeutic strategy that collectively targets the functionally linked HER2 and Notch pathways.

 

Applications


  • Combination therapy for DCIS patients following surgical tumor removal.
  • Classification of DCIS patients according to HER2 Notch activation patterns to identify patients with increased risk of relapse after surgery.
  • Diagnostic antibodies to NRG4 to screen for cancer cell subtypes that express/over-express NRG4.
  • NRG4 fusion conjugates, where NRG4 acts as a vehicle to direct the conjugate to cells specifically expressing the receptor ErbB4.

 


Advantages


  • Targeted cancer therapies will give doctors a better way to tailor cancer treatment.
  • Targeted cancer therapies hold the promise of being more selective, thus harming fewer normal cells, reducing side effects, and improving the quality of life.
  • The proposed treatment strategy may prove beneficial in DCIS patients with poor prognosis.

 


Technology's Essence


The HER2/Neu oncogene, a member of the HER/ErbB signaling network, encodes a receptor-like tyrosine kinase, whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. Pre-invasive lesions, such as DCIS, overexpress HER2 at higher frequency than invasive ones. Another signal transduction pathway critical for breast cancer progression comprises Notch family receptors and their membrane-bound ligands. In the current technology, a team of researchers from the Weizmann Institute of Science uncovered that overexpression of HER2 in a novel experimental model of DCIS leads to transcriptional upregulation of Notch pathway components, resulting in enhanced tumor cell survival and proliferation. Combined treatment with HER2 and Notch pathway inhibitors resulted in decreased proliferative and tumorigenic potential. The current technology offers specific and combined targeting of HER2 and Notch pathways for DCIS treatment. This approach may also be tailored for DCIS patients with enhanced co-expression of HER2 and Notch.

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  • Prof. Yosef Yarden
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
1610
A novel method for increasing Insulin content in pancreatic beta cells. In healthy individuals, Insulin is produced by beta cells of the pancreas. In people with type 1 diabetes mellitus (T1DM), these cells do not produce enough Insulin to effectively fine-tune blood sugar levels. In the US alone...

A novel method for increasing Insulin content in pancreatic beta cells.

In healthy individuals, Insulin is produced by beta cells of the pancreas. In people with type 1 diabetes mellitus (T1DM), these cells do not produce enough Insulin to effectively fine-tune blood sugar levels. In the US alone there are up to 3 million affected individuals with 30,000 new cases diagnosed each year. Worldwide, T1DM incidence has been increasing in recent years by 2% to 5%. Traditionally treated by multiple daily injections of recombinant Insulin, T1DM management represents a significant burden to both patients and the healthcare system. Recent data estimate that T1DM costs the US ~$15 billion annually in medical costs and lost income. Thus, novel therapeutic approaches to amplify Insulin production in diseased beta cells or to replace them entirely are in great need. The present technology describes a cell-based method to enhance beta cell differentiation and Insulin production by the downregulation of a pancreas-enriched microRNA.

 

Applications


  • Cell replacement therapy: directed differentiation of stem cells towards a beta cell fate followed by transplantation of these engineered cells into patients.
  • These methods can potentially be applied to other Insulin deficiency-related conditions such as diabetes mellitus type 2, metabolic syndrome and obesity.

Advantages


  • Simple and robust method for accelerating beta cell differentiation.
  • Cell base therapy for diabetes.
  • Increasing Insulin level.

Technology's Essence


A research team headed by Dr. Hornstein from the Weizmann Institute has discovered an essential role for microRNA-7 (miR-7), a microRNA that is highly and selectively expressed in the endocrine pancreas, in the regulation of beta cell differentiation. By down-regulating the expression of miR-7, the researchers were able to accelerate beta cell differentiation, and concomitantly to augment their Insulin production rate. The data gained from these studies can be further utilized in cell-based therapy applications to restore Insulin production in damaged beta cells, or alternately to replace these cells with stem cells coaxed to differentiate towards a beta cell fate.

 

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  • Dr. Eran Hornstein
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
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
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
1621
Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases,...

Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases, age-related macular degeneration and atherosclerosis. The global market for angiogenesis stimulators and inhibitors is forecast to reach ~US $50 billion by the year 2015. Most of the currently marketed angiogenesis regulators, such as Avastin, typically display modest efficacy and therefore further highlight the great need for the development of novel therapeutics. The current technology presents a novel method to treat angiogenesis-related disorders by modulating apolipoprotein B (ApoB).

Applications


  • ApoB is a potential therapeutic target for the treatment of cancer and other non-neoplastic diseases.
  • ApoB levels may serve as a biomarker for cancer metastasis.

Advantages


  • The anti-angiogenic effect of LDL administration was demonstrated in vivo, in zebrafish models, as well as in vitro, in relevant human cells lines.
  • Regulation of ApoB levels may be applied to treat a broad range of angiogenesis-dependent diseases.
  • Detection of ApoB levels can be readily achieved by analysis of body fluids such as blood and plasma.

Technology's Essence


Using a high-throughput genetic screen for vascular defects in zebrafish, researchers at the Weizmann Institute of Science have identified a genetic mutation that leads to excessive angiogenesis. The mutated gene is responsible for the assembly of ApoB-containing lipoproteins such as LDL, otherwise known as the ‘bad’ cholesterol. The group has found that low levels of LDL promote the formation of new blood vessels by directly interacting with the VEGF pathway. The outlined technology offers methods to modulate the levels of ApoB in order to stimulate, or inhibit angiogenesis, dependent on the therapeutic strategy. For example, inhibition of angiogenesis by increasing ApoB levels may repress tumor growth and attenuate its metastatic potential. In another application of this technology, increased circulating levels of ApoB can serve as a biomarker for the overproduction of blood vessels, thus enabling early diagnosis of pathogenic states in angiogenesis-dependent diseases.

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  • Dr. Karina Yaniv
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
1664
Neuroinflammation is well established as a key secondary injury mechanism following CNS trauma, such as traumatic brain/spinal injury or ischemic stroke, and it has been long considered to contribute to the damage sustained and fatal outcomes following brain injury. Early inflammatory events enhance...

Neuroinflammation is well established as a key secondary injury mechanism following CNS trauma, such as traumatic brain/spinal injury or ischemic stroke, and it has been long considered to contribute to the damage sustained and fatal outcomes following brain injury.
Early inflammatory events enhance brain damage, yet they provide the framework for later inflammatory events that enhance tissue remodeling and are crucial for tissue recovery.
A major unmet need in the field is a targeted treatment that would down regulate the damaging events of inflammation, while maintaining reparative functions. 
Altering between CNS microglia pro and anti-inflammatory activation states is at the core of injury-induced neuroinflammation and presents an opportunity to specifically tilt the balance towards anti-inflammatory and repair processes.
The present discovery elucidates the mechanisms that lead to injury-induced microglia over-activation and proposes IFN-? as a therapeutic strategy to induce microglia resolving state and relive inflammation. 

Applications


Anti-inflammatory treatment following CNS injury

Advantages


  • Targeted therapy – avoids general immuno-suppressive side effects
  • Based on a well understood molecular mechanism
  • May allow relatively large therapeutic window – according to proof-of-concept  preliminary experiments

Technology's Essence


Resident microglia are the major specialized innate immune cells of the central nervous system (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 an inflammation-resolving phenotype (M2-like phenotype) in a timely manner, often resulting in self-perpetuating local inflammation and tissue destruction beyond the primary insult.
Prof. Schwartz and her team 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 (IRF7).  Their results demonstrate that restoring Irf7 expression by IFN-? (a known IRF7 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, when administrated 24h following the primary insult, proposing a relatively large therapeutic window.

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  • Prof. Michal Schwartz-Eisenbach

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