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

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

Applications


 


Advantages


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

Technology's Essence


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

 

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  • Prof. Yoram Groner
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
1650
Efficient Production of natural Astaxanthin in bioengineered bacteria is a game changer for the nutraceuticals industry. The market-pull for natural Astaxanthin is much greater than the supply. Synthetic Astaxanthin is produced from petrochemical sources; it contains unwanted stereoisomers and is...

Efficient Production of natural Astaxanthin in bioengineered bacteria is a game changer for the nutraceuticals industry. The market-pull for natural Astaxanthin is much greater than the supply. Synthetic Astaxanthin is produced from petrochemical sources; it contains unwanted stereoisomers and is rejected by consumers who prefer natural Astaxanthin. Production of natural Astaxanthin in microalgae is laborious, expensive, and time-consuming.
Researchers at the Weizmann Institute used a combinatorial approach to construct bioengineered operons capable of modulating the expression levels of enzymes involved in the production of Astaxanthin. By combinatorial pairing of these genes in E. coli, they achieved natural Astaxanthin production 4-fold higher than previously reported.
The innovative method can challenge the deficiencies of natural Astaxanthin production in microalgae. Following scale-up and industrial development of the proprietary process, production of natural Astaxanthin has the potential to be considerably cheaper and competitive with the cost of synthesizing Astaxanthin.

Applications


  • Cost-effective Production of natural Astaxanthin for the nutraceuticals industry, animal feed industry, and others.
  • A doorway to the generation of many future products in E. coli, specifically metabolites that are produced in elaborate metabolic pathways.

Advantages


  • Full control over carotenoid accumulation profile.
  • Cheaper, straightforward generation of Astaxanthin in E. coli as opposed to generation in algae which involves high raw materials cost, land usage, air emissions etc.
  • Natural Astaxanthin as opposed to synthetic, uncontaminated with intermediate compounds and stereoisomers.

Technology's Essence


At Dr. Ron Milo’s lab researchers employed a method that uses the relatively short Ribosome Binding Site (RBS) sequence in a combinatorial manner. The methodology involves combinatorial pairing of target genes (Astaxanthin metabolic pathway enzymes) with a small set of RBS sequences and assembling them into a library of synthetic operons to explore protein expression space and to locate desired phenotypes in bacteria.
The researchers used a small set of RBS sequences to modulate in parallel the protein expression levels of multiple genes over several orders of magnitude. Using this approach, they were able to efficiently scan a large fraction of the Astaxanthin metabolic expression space with a manageable set of tested genotypes.

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  • Prof. Ron Milo
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
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
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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  • Prof. Karina Yaniv
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
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
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
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

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