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Scientist
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
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
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
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
1602
A novel technology for robust downregulation of bacterial genes.RNAi (RNA interference) is a powerful method for downregulation of gene expression in eukaryotic systems. RNAi-based technologies are extensively applied as scientific research tools, as well as actively explored as promising therapeutic...

A novel technology for robust downregulation of bacterial genes.RNAi (RNA interference) is a powerful method for downregulation of gene expression in eukaryotic systems. RNAi-based technologies are extensively applied as scientific research tools, as well as actively explored as promising therapeutic agents. However, although an efficient way to dowregulate bacterial and microbial gene expression has been long sought after, RNAi is not applicable in these species. The present technology offers a rapid and simple means to silence gene products in prokaryotic systems.

Applications


  • Treatment of bacterial infection, by targeting bacterial genes vital for antibiotic resistance or bacterial virulence.
  • Enhanced biofuel production by targeting genes that interfere with ethanol and/or hydrogen biosynthesis.
  • Generation of improved bacterial strains for the diary industry (e.g. phage-resistant strains).
  • Discerning prokaryotic gene function by silencing the expression of the gene product.

Advantages


  • The present technology may offer means to treat antibiotics-resistant strains.
  • Because CRISPR-based technology does not involve ‘classical’ genetic engineering, the resulting products do not require labeling as 'genetically modified'.
  • CRISPR-based technology system allows for the development of a rapid, scalable and high-throughput platform to probe the function of genetic circuits in prokaryotes.

Technology's Essence


CRISPR (clusters of regularly interspaced short palindromic repeats) is a recently discovered anti-viral system that functions as the prokaryotic-equivalent of the adaptive immune system. CRISPR provides bacteria with protection against foreign genetic elements such as viruses by incorporating short stretches of invading DNA sequences in genomic CRISPR loci. These integrated sequences are thought to function as a genetic memory that prevents the host from being infected by the viruses and other genetic elements containing this recognition sequence. A team of researchers at the Weizmann Institute, headed by Dr. Rotem Sorek, has developed a unique technology to gain robust and rapid silencing of prokaryotic gene expression by exploiting the CRISPR system capacity to efficiently downregulate gene products. This potent technology can potentially be utilized in a broad range of areas such as in the agriculture, food and pharmaceutical industries as well as in the scientific research arena.

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  • Prof. Rotem Sorek
1639
Sphingolipid-peptide conjugates with potent anti-viral activity. According to the WHO, 34 million people around the world are afflicted with HIV, the causative agent of AIDS, with approximately 2.5 million new infections diagnosed each year. The development of new drugs against HIV has been the focus...

Sphingolipid-peptide conjugates with potent anti-viral activity.

According to the WHO, 34 million people around the world are afflicted with HIV, the causative agent of AIDS, with approximately 2.5 million new infections diagnosed each year. The development of new drugs against HIV has been the focus of intense research since its discovery. The market size of HIV-1 treatment is indeed significant with drug sales expected to rise from $13.3 bn in 2011 to $16.7 bn in 2020 in the Western world alone. Nevertheless, there is a highly unmet need for innovative HIV treatment approaches. One such approach is the design of early entry inhibitors that are able to block viral fusion and entry into the host cell. The present technology presents sphingolipid-peptide conjugates (sphingo-peptides) with a potent capacity to interfere with HIV viral fusion.

 

Applications


·         Design of novel HIV therapeutics.

·         Extension of half-life of current HIV fusion inhibitors.

·         Topical blockers of viral transmission.

 


Advantages


  • Blocking viral entry prevents all subsequent intracellular steps, most importantly viral genome integration.
  • Sphingolipid conjugates improve efficacy and half-life of current HIV fusion inhibitors.
  • Sphingopeptides were shown to be effective against certain drug-resistant strains.
  • A unique mode of action that reduces the likelihood of developing resistant strains.

Technology's Essence


The first step in the life cycle of enveloped viruses such as the HIV-1 is entry into their host cells by membrane fusion. Therefore, the dynamic process of HIV fusion and entry represents a valid target for rational drug design. A team of researchers at the Weizmann Institute has developed unique sphingolipid-peptide conjugates that block the fusion of the HIV virus to its host cell membrane. Remarkably, the sphingolipid moiety endowed potent anti-viral activity to otherwise poorly and nonactive peptides. Moreover, the sphingo-peptide inhibitors were shown to be highly effective against both wt as well as drug-resistant HIV strains.

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  • Prof. Yechiel Shai
1611
Novel HIV-derived peptides for the treatment of T-cell related disorders.Autoimmune diseases affect millions of individuals worldwide and the cost of these diseases, in terms of actual treatment expenditures and lost productivity, is measured in billions of dollars annually. Uncontrolled activation of...

Novel HIV-derived peptides for the treatment of T-cell related disorders.Autoimmune diseases affect millions of individuals worldwide and the cost of these diseases, in terms of actual treatment expenditures and lost productivity, is measured in billions of dollars annually. Uncontrolled activation of T cells is a hallmark of many autoimmune diseases; prominent among these are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Type I diabetes. T cells also play a cardinal role in the rejection for organ transplantation or graft versus host disease. Currently available therapies such as immunosuppressive drugs suppress the patient's entire immune response, thereby increasing the risk of infection, and can cause toxic side effects to non-lymphoid tissues. The development of new immunosuppressive agents capable of selectively inhibiting the activation of T lymphocytes with minimal side effects is therefore desirable. The present invention provides novel peptides endowed with immunosuppressive activity, for the treatment of T-cell related conditions such as autoimmune, inflammatory and graft rejection disorders.

 

Applications


Treatment of various T-cell mediated pathologies including:

  • Autoimmune diseases.
  • Inflammatory disorders.
  • Graft rejection and graft-versus-host disease (GVHD).

 


Advantages


  • The peptides exhibit minimal toxicity.
  • The peptides are about 20 times more potent than the strongest peptide reported from the HIV envelope proteins.
  • The peptides are less hydrophobic than other gp41-derived peptides and as such are more readily soluble in aqueous solution.

Technology's Essence


A team of scientists from the Weizmann Institute has developed peptides, derived from the ectodomain of the HIV gp41 envelope protein, that are able to effectively inhibit T cell activation. These peptides are 20-fold more potent as immunosuppressive peptides compared to other HIV-derived immunosuppressive peptides. The novel gp41-derived peptides robustly attenuated autoimmune disease in vivo, as shown in an experimental autoimmune encephalomyelitis (EAE) animal model, while demonstrating minimal toxic effect in both in vivo and in vitro studies. Furthermore, the novel peptides are remarkably less hydrophobic than other HIV-derived peptides, and therefore can readily dissolve, facilitating their administration as therapeutic agents.

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  • Prof. Yechiel Shai
1641
A novel RNA-seq method enables unbiased identification and characterization of cell populations from low-quantity samples (~1000 cells). Utilizing tag-free FACS sorting, researchers at the Weizmann Institute are able to create single cell cDNA libraries in under two hours and at a low cost. As...

A novel RNA-seq method enables unbiased identification and characterization of cell populations from low-quantity samples (~1000 cells). Utilizing tag-free FACS sorting, researchers at the Weizmann Institute are able to create single cell cDNA libraries in under two hours and at a low cost.

As personalized medicine requires analysis of minute RNA quantities from patients, there is a great need for unbiased and comprehensive analysis of cells’ transcriptome from low-quantity samples.  Attaining simultaneous observation on millions of cells in their native context is currently a laborious and expensive process. Therefore an unbiased functional characterization of In vivo cell populations is of great demand.

The Researchers have successfully addressed this challenge in a top down fashion by focusing on cell types. Using broad sampling of single cell transcriptional states from multi-cellular tissues they could reconstruct biological functions. They suggest a straightforward path to construct an unbiased map of functional cell states that are sampled directly from their native context. Thus they reveal a new methodology for microscopic analysis of the transcriptome in heterogeneous tissues.

Applications


The innovative technology has potential applications in basic research, personalized medicine and clinical diagnostics -

·         Kits for single cell transcriptome analysis of FACS output.


Advantages


·         Dramatic reduction is costs and labor.

·         High resolution, robust.

·         Top down, unbiased.

·         No need to use markers.


Technology's Essence


This technology combines an automated 384-well cell capture and library preparation assay, two-tier molecular and cellular labeling and efficient poly-A tailed RNA conversion.  Amplification and sequencing of multiplexed libraries is achieved with 1000 cells in a single experiment.  Notably, each read in this method is directly interpretable as representation of a single RNA molecule from a specific single cell. The result is highly practical profiling of large cells samples. This further enables robust characterization of subpopulations’ functional state (at a resolution of 10 cells or 1% of 1000 cells sample).

Moreover the researchers have developed a computational framework that aggressively filters noise and potential biases in the data using randomized molecular labels (RMT) and controls for different sources of amplification and inter-cell contamination errors.
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  • Prof. Ido Amit
  • Prof. Ido Amit
1618
A novel method is disclosed here for boosting the immune response, useful not only for the treatment of microbial and chronic viral infections, but also for activating the immune system against cancer cells. TLR-4 is a central player in the innate immune system as it specifically recognizes...

A novel method is disclosed here for boosting the immune response, useful not only for the treatment of microbial and chronic viral infections, but also for activating the immune system against cancer cells. TLR-4 is a central player in the innate immune system as it specifically recognizes lipopolysaccharide (LPS), the major cell wall component of Gram-negative bacteria, and activates the immune system. Newly developed peptides derived from the N-terminus of a TLR-4 trans-membrane domain are capable of activating TLR-4 mediated immune response, thus useful both as stand-alone treatments and as vaccine adjuvants, increasing the immunogenicity of an antigen in a vaccine. Taken together, the newly developed peptides are useful for the treatment and prevention of a large variety of infections, such as microbial (e.g. Salmonella, Escherichia, Pseudomonas), viral (including HIV, Hepatitis and Influenza) and fungal infections. Further, they are useful in the treatment and prevention of a wide variety of cancers.

Applications


  • Treatment for a wide variety of infectious diseases and cancers.
  • Prophylaxis for a wide variety of infectious diseases and cancers, as an adjuvant administered together with specific antigen.

Advantages


  • Treats a wide variety of bacterial, viral and fungal infections.
  • Suitable both as a treatment and prophylaxis.
  • Boosts the endogenous immune system
  • Peptides are easy to synthetize and purify
  • Patient-friendly administration, either systemic or local.

Technology's Essence


The technology is based on the discovery that peptides derived from the N-terminus of a TLR-4 TM domain or their analogs are capable of activating TLR-4 mediated immune response. These peptides activate TLR-4 receptor, possibly by dimerizing within the cell membrane and stabilizing the TLR-4 dimer. Through TLR-4 activation, these peptides activate macrophages to secrete TNF-alpha, thereby stimulating the immune system. In addition, the ability of these peptides to modulate the immune system's innate response renders them useful as vaccine adjuvants, increasing the immunogenicity of an antigen in a vaccine.

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  • Prof. Yechiel Shai
1546
Improvement of protein production by modulating the tRNA pool. For maximal heterologous expression of proteins per host cell, the optimal level of expression of genes needs to be addressed. The science and art of expressing a gene from one species in another often amounts to modifying the codons of the...

Improvement of protein production by modulating the tRNA pool. For maximal heterologous expression of proteins per host cell, the optimal level of expression of genes needs to be addressed. The science and art of expressing a gene from one species in another often amounts to modifying the codons of the gene, and supplementing the host with specific tRNAs. Yet the full challenge of heterologous expression is not only to maximize expression per host cell, but also to minimize the burden on the host. The outlined invention describes a universally conserved profile of translation efficiency along mRNAs, based on the adaptation between coding sequences and the tRNA pool, to improve heterologous gene expression and thus protein production.

Applications


  • Improvement of the yield and success rate of recombinant protein production.

Advantages


  • Protein expression levels can be artificially increased
  • Minimization of the burden on the host

Technology's Essence


The translation efficiency profile of a gene is defined, for each codon position, as the estimated availability of the tRNAs that participate in translating that codon. The profile is high at codons that correspond to abundant tRNAs and low at codons that correspond to rare tRNAs. In this invention it is predicted that the first ~30-50 codons of genes appear to be translated with a low efficiency “ramp”, while the last ~50 codons show highest efficiency. The “ramp” serves as a late stage of initiation and is an optimal and robust means to reduce ribosomal traffic jams, thus minimizing occupation of free ribosomes, ribosomal abortions and, ultimately, the cost of protein expression. Implementation of appropriate ramping in heterlogous proteins, given the host?s tRNA pool, might improve the yield of expressed recombinant proteins.

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  • Prof. Yitzhak Pilpel
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
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
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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