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Technology Name
Briefcase
Scientist
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
1673
CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical...

CF is the most common autosomal recessive disorder in western countries, affecting approximately 30,000 people in the US alone. A major risk in CF arises from chronic bacterial lung infections, affecting 80% of CF patients by the age of 25. Bacterial lung infections are also of major clinical importance in patients with chronic obstructive pulmonary disease (COPD), trauma, burn wounds, sepsis, or in patients requiring ventilation. The infections are currently treated with antibiotics, which rapidly become inefficient as resistant bacteria strains arise. The present technology suggests a novel therapeutic approach for the prevention and treatment of bacterial lung infection in susceptible populations, especially CF patients

Applications


  • Alternative treatment for bacterial lung infections.
  • A prophylaxis for patients susceptible to bacterial lung infections

Advantages


  • A novel therapeutic approach to prevent or cure bacterial lung infection.
  • The new therapy is based on reinforcement of the physiological innate immunity rather than on antibiotics.
  • The new therapy can be easily administered, via inhalation.
  • FTY720, a SPH analog, is already in clinical use for treating multiple sclerosis.

Technology's Essence


Sphingosine (SPH), a natural bactericidal agent which acts as a part of the human innate immune system in the skin, was found to be an effective treatment and prophylaxis for bacterial lung infections in cystic fibrosis (CF) mice. The new technology is based on the discovery that both CF human patients and CF mice display reduced rates of SPH in the airways. Moreover, normalizing SPH levels by inhalation prevents or cures the infections in CF mice, thus rendering SPH and its analogs a potent therapeutic agent for CF patients, an alternative to antibiotics.

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

A potent combination therapy against non-invasive breast cancer

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

 

Applications


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

 


Advantages


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

 


Technology's Essence


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

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

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

Applications


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

Advantages


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

Technology's Essence


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

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

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

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

 

Applications


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

Advantages


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

Technology's Essence


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

 

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

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

Applications


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

Advantages


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

Technology's Essence


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


 

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  • Prof. Irit Sagi
  • Prof. Irit Sagi
1616
Existing treatments against cancer are non-sufficiently selective. Immunotherapy based treatment offers highly selective and efficient solution to this problem. A promising approach in Immunotherapy is adoptive cell therapy (ACT). In ACT, therapeutic lymphocytes are administrated to patients in order...

Existing treatments against cancer are non-sufficiently selective. Immunotherapy based treatment offers highly selective and efficient solution to this problem.
A promising approach in Immunotherapy is adoptive cell therapy (ACT). In ACT, therapeutic lymphocytes are administrated to patients in order to treat a disease. In this process antibody-type cells are generated ex vivo, and then infused to the patient. By this technology the cells can be redirected against specific tumors via genetic engineering, using chimeric receptors.
Currently ACT is logistically and economically challenging since it is limited by the used of the patients’ own cells. Another key concern is safety, due to the danger that the allogeneic cells will be rejected by the patient, or will attack the patient.
In cancer, use of tumor specific, chimeric receptor redirected allogeneic T cells can transform ACT into a standardized, off-the shelf therapy. Overall this method proposes a safe and effective adoptive therapy using allogeneic cells while avoiding the use of bone marrow transplantation (BMT).

Applications


  • Cancer immunotherapy

Advantages


  • Off the shelf, standard treatment
  • Safe
  • Effective
  • No bone marrow transplantation (BMT) is required

Technology's Essence


A novel approach for adoptive immunotherapy using fully MHC-mismatch allogeneic T cells. These cells are redirected with tumor specific non-MHC-restricted antibody-based chimeric antigen receptor (T-bodies) in the absence of Graft-versus-host disease (GVHD). In order to create a standardize treatment, the redirection of T cells can be done through an antibody-based chimeric antigen receptor (CAR), thus creating ‘universal effector T cells’. This is based on a combination of of MHC-mismatched allogeneic T-cells with an MHC unrestricted chimeric antigen receptor. These cells would recognize their target independently of MHC restriction, therefore applied as an ‘off-the shelf’ immunotherapy. Regarding the second challenge of avoiding GVHD, by using a controlled lymphodepletion the researchers were able to create therapeutic window during which the allo-T-body cells could destroy the tumor before being themselves rejected.

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  • Prof. Zelig Eshhar
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
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

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