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Biotechnology, Pharma and Diagnostics

Category
Technology Name
Briefcase
Scientist
1774
A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies. Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect...

A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies.

Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect on this specific malignancy. The reason is that lung cancer cells regularly acquire resistance through multiple compensatory mechanisms, including secondary (new) mutations in receptors which block the effects of TKIs; up-regulation of specific genes; or rewiring of signaling networks.

The current technology works around these compensatory mechanisms by using a mixture of antibodies that function in a synergistic manner, to effectively and specifically target lung cancer cells, without affecting healthy cells.

Applications


·         Treatment of non-small cell lung cancer (NSCLC).

·         A method for augmenting currently available TKIs.


Advantages


·         Specificity – treatment was able to target EGFR-mutated NSCLC cancer cells, and showed no effect on healthy cells.

·         Effective – able to strongly inhibit NSCLC cancer cell lines and inhibit xenografted NSCLC cells in a mouse model.

·         Novel Approach – utilizing data derived from both clinical and laboratory research to devise a method for counteracting compensatory mechanisms of cancer cells.


Technology's Essence


Prof. Yosef Yarden and his group have discovered that by simultaneously inhibiting multiple receptors, namely HER2 and HER3 along with EGFR, they could effectively circumvent the compensatory mechanisms and inhibit NSCLC cell growth. This was determined using a combination of clinical, in vitro, and in vivo data. In addition, in vivo experimental work included xenograted mouse models where only the triple combination of antibodies effectively reduced tumor volume relative to standard mAb treatments.

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  • Prof. Yosef Yarden
1790
A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix. Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for...

A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix.

Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for vulnerable populations such as children and seniors. This is due to the host immune response which can damage the lung tissue, serving as a prime target for secondary infections. Consequently, there is a need for a method that provides better control over inflammatory response and reduces tissue damage caused by the host immune response to an infection.

Prof. Irit Sagi’s research team has discovered that by specifically inhibiting MT1-MMP they can limit tissue damage in the lungs of mice, help prevent secondary infections, and subsequently improve overall survival rates.  

Applications


·         Limiting tissue damage for the prevention and treatment of secondary infections.


Advantages


·        Novel mechanism – targeting MT1-MMP to limit inflammation due to an immune response, rather than targeting the pathogen directly.

·        Usage of an antibody for prophylaxis or treatment

·        Synergism – possibly combined with an anti-pathogen agent to assist in treatment. 

·        Better outcomes – reduction of tissue damage and inhibition of secondary infections improves overall survival rates.


Technology's Essence


The research team of Prof. Irit Sagi has shown a novel mechanism of treating and preventing secondary infections by inhibition of MT1-MMP using an anti-MT1-MMP antibody. The team used mice as an infection model. They performed in vitro experiments on extracted mice lungs to characterize MT1-MMP’s role in the infection pathology. They also calculated survival rates following both primary and secondary infections of mice, with and without inhibition of MT1-MMP. Which showed that the inclusion of the anti-MT1-MMP antibody improved overall survival rates in the infected mice.

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  • Prof. Irit Sagi
1776
A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient. Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the...

A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient.

Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the same since the 1970’s, involving systemic chemotherapy treatment, and surgery. The problem of limited treatment options is further exacerbated due to the high proportion of patients who relapse following chemotherapy.

The group of Prof. Yosef Yarden at the Weizmann Institute of Science (WIS) has discovered that amphiregulin (AREG) levels are elevated in the body fluids of a high percentage of ovarian cancer patient samples they tested. Prof. Yarden’s group has found that by intercepting AREG in combination with chemotherapy, they were able to inhibit the growth of ovarian tumors.

Applications


·         Inhibiting growth of ovarian cancer.

·         Possible treatment for other types of cancer.

·         Using AREG as a possible theranostic for ovarian cancer.


Advantages


·         Innovative Target – Intercepting the EGF-ligand AREG.

·         Flexible – Anti-AREG mAbs could be used alone or in combination with current chemotherapy treatments for different malignancies.


Technology's Essence


Prof. Yosef Yarden and his group have found that the EGFR ligand, Amphiregulin (AREG) was elevated in the bodily fluids of 80% of cancer patient samples tested. These results were further supported by in vitro work with varying cancer cell lines, again showing elevated AREG concentrations in their media. The Yarden group then generated an anti-AREG antibody, and performed experiments in vivo using mouse models xenografted with ovarian cancer cells. The results show that co-administering the anti-AREG antibody re-sensitized the tumors to standard chemotherapy treatments. This emphasizes the value of AREG not only as an anti-cancer target but also as a possible diagnostic marker.  

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  • Prof. Yosef Yarden
1760
Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with...

Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with issues of harsh side-effects of using said drugs.

Currently one of the most problematic antibiotic resistant bacterium is methicillin-resistant Staphylococcus aureus (MRSA). MRSA is becoming prevalent in hospitals and care homes, increasing the risk associated with hospitalization and invasive medical procedures. Therefore there is an urgent need to develop new antibiotics to combat MRSA.

The present technology from the lab of Nobel Prize winning Prof. Ada Yonath offers a tool in designing and developing new types of novel antibiotics. It is a high resolution crystal structure of the large ribosomal (50S) subunit from Staphylococcus aureus. The structure is based on a pathogenic strain giving new insight and capacity to target specifically the bacterium (Eyal Z, et al. (2015) Proc Natl Acad Sci and Eyal Z, et al. (2016) Sci. Rep.).

Applications


·         Designing and developing new types of antibiotics.

·         Computational screening of chemical libraries, reducing the number of physical compounds to screen.

·         Improving overall understanding of the ribosome in S. aureus.

·         New potential antibiotics binding sited which are species specific.


Advantages


·         High Resolution – the structure gives high detail and possible target positions for antibiotics.

·         Crystal Structures soaked with antibiotics – certain antibiotics have been soaked with the structure giving insight in how they interact with the ribosome, improving rational design of new antibiotics.

·         Structure based on pathogenic bacterium – improving targeting of antibiotics, as current bacterial ribosomal structures are based on non-pathogenic species.


Technology's Essence


The invention is a high resolution crystal structure of the large ribosomal subunit from the pathogenic S. aureus. The crystal structures importance is that it originates from a pathogenic species allowing for a high-degree of specificity in targeting the S. aureus ribosome. Rather than the currently available ribosomal structures based on non-pathogenic bacteria, where small differences between species may limit the effectiveness in a designed antibiotic. The importance of the technology is that MRSA (methicillin-resistant S. aureus), is becoming more common place in hospitals, care homes, and even in the agricultural sector. Thus there is a clear need for new types of antibiotics that can help to counteract the ever growing problem of bacterial antibiotic resistance.  

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  • Prof. Ada Yonath
1549
A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one...

A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.

Applications


  • Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)

Advantages


  • Effective blockade of the tumorigenic action of ErbB-specific ligands
  • The combination protocol may enhance the sensitivity to chemotherapy

Technology's Essence


In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.

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  • Prof. Yosef Yarden
1736
Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production. Improvement in the...

Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production.

Improvement in the metabolic pathway related to carbon fixation would have great value in increasing crop yields, synthesizing high value compounds in algae, and developing means in removing CO2 from the atmosphere to combat climate change.

The present technology is an engineered E. coli with a carbon fixation pathway. The unique innovation can be used to efficiently screen the activity of RuBisCO, the most abundant carbon fixing enzyme on earth, which is further applicable to improving biomass production in different photosynthetic organisms such as plants and algae.

Applications


·      Powerful platform for screening and improving various enzymes in the carbon fixation process.

·      Unique metabolic pathway for use in Synthetic Biology applications.

·      Possible Carbon Credits for developing improved means of carbon fixation.


Advantages


·      E. coli is fast growing and easily manipulated by various genetic tools.

·      Novel source of biomass production.

·      Potentially low cost R&D system.


Technology's Essence


The technology functions by the recombinant insertion of two enzymes from the Calvin-Benson-Bassham (CBB) into E. coli, kinase prk and the carboxylating enzyme RuBisCO. With further modifications, the engineered E. coli’s metabolism was divided into two subsections. First a carbon fixing metabolism that can incorporate inorganic CO2 into sugar production, the second subsection consumes organic pyruvate to produce energy to drive the aforementioned carbon fixing cycle. Subsequently the technology is overall carbon neutral, but is an inexpensive and fast platform for screening improvements in the CBB carbon fixation pathway.

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  • Prof. Ron Milo
1712
  • Prof. Yechiel Shai
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
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
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
1733
The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change...

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

Applications


  • Inflammation
  • Immune diseases

Advantages


  • Effective
  • Safe

Technology's Essence


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

 

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  • Prof. Rony Seger

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