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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
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
1628
New generation of superior nature-inspired therapeutics for treating inflammation.Inflammation is characterized by elevated levels of TNF-?. Neutralizing TNF-? activity was shown to be beneficial for patients with chronic autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and...

New generation of superior nature-inspired therapeutics for treating inflammation.Inflammation is characterized by elevated levels of TNF-?. Neutralizing TNF-? activity was shown to be beneficial for patients with chronic autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, current treatments of such conditions include general anti-inflammatory and immunosuppressive drugs that are of limited effectiveness and may cause serious side effects. Another class of drugs includes targeted therapies directed against TNF-?, that are associated with serious infections including tuberculosis (TB) and sepsis as well as increased risk of cancer in some cases. Thus, there is an urgent need for highly selective, safer and more effective drugs for inflammatory conditions that involve TNF-? as a key mediator. The present technology introduces a novel generation of candidate drugs that selectively inhibit the processing of TNF-?, thereby preventing it from exerting its pro-inflammatory properties. This technology provides a framework for the development of safer and more effective therapeutics for IBD and related autoimmune disorders.

Applications


  • Treatment of autoimmune inflammatory conditions such as IBD and RA.
  • Treatment of neuroinflammatory conditions such as multiple sclerosis (MS).
  • Treatment of other inflammatory mediated diseases such as psoriasis, systemic sclerosis and ankylosing spondylitis.
  • All MMPs and ADAMs proteases possess an autoinhibitory pro-domain and therefore this technology can be broadened to other MMP and ADAM targets.

Advantages


  • TACE pro-domain is highly potent and efficient.
  • TACE pro-domain is metabolically stable, unlike small molecule inhibitors of TACE.
  • Targeting TACE through nature-inspired protein design may constitute a safer approach to combat TNF-? induced inflammation.
  • Unlike non-specific small molecule inhibitors, which target the conserved catalytic zinc site of TACE, TACE pro-domain shares little homology to other MMPs, making it a good candidate for specific inhibitor of TACE.

Technology's Essence


The A disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor-? converting enzyme (TACE), has been defined as the major shedding protease for a broad range of substrates predominantly the key immuno-regulatory cytokines TNF-?. Cleavage by TACE renders TNF-? pro-inflammatory, highlighting ADAM17 as a rationale target for treatment of autoimmune diseases such as IBD and arthritis. A team of researchers at the Weizmann institute headed by Prof. Irit Sagi, has employed a sophisticated approach towards TACE targeting by exploiting its autoinhibitory pro-domain as a platform for the ‘smart design’ of TACE selective natural inhibitors. The therapeutic potential of TACE pro-domain was demonstrated in IBD mouse models, where TACE pro-domain administration showed significant improvement in multiple parameters such as reduced mortality and weight lost, in a dose dependent manner. Additional in vivo studies demonstrated that the TACE pro-domain is highly stable in vivo and harbors specificity towards the activated immune cells located in colon lesions. Thus, the novel TACE inhibitor presented in this technology leads to significant therapeutic effects and is beneficial in controlling inflammation in IBD disease manifestations in mice.

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

A potent combination therapy against non-invasive breast cancer

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

 

Applications


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

 


Advantages


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

 


Technology's Essence


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

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

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

Applications


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

Advantages


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

Technology's Essence


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

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

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

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

 

Applications


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

Advantages


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

Technology's Essence


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

 

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

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

Applications


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

Advantages


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

Technology's Essence


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


 

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  • Prof. Irit Sagi
  • Prof. Irit Sagi
1245

Applications


The novel DNA Aptamer is a promising candidate for therapeutic as well as diagnostic uses: Therapeutic: A novel therapy for Influenza Diagnostics: Detection of Influenza infection in vertebrates such as avian, swine and human

Technology's Essence


Scientists at the Weizmann Institute of Science describe a novel oligonucleotide, also known as an Aptamer, which has been designed to complement the receptor-binding region of the influenza haemagglutinin molecule. It was constructed by screening a DNA library and processing by the SELEX procedure. This DNA Aptamer comprises of a polynucleotide sequence that can bind to a polypeptide within the binding region of the influenza virus to the host cell. The proposed mode of action of this Aptamer is by blocking the binding of influenza virus to target cell receptors and consequently preventing the virus invasion into the host cells. Aptamer is capable of inhibiting the haemagglutinin capacity of the virus and the viral infectivity in vitro. Furthermore, it was shown in an animal model to inhibit viral infection by different influenza strains, as manifested by up to 99% reduction of virus burden in the lungs of treated mice.

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  • Prof. Ruth Arnon
1527
New peptides for improving the recruitment of stem cells for transplantation. Blood cancers (leukemia, lymphoma and myeloma) are very common: they accounted for nearly 9.5 percent of deaths in the US from cancer in 2009. Stem cell transplantation, which aims to restore the function of the marrow, is an...

New peptides for improving the recruitment of stem cells for transplantation.

Blood cancers (leukemia, lymphoma and myeloma) are very common: they accounted for nearly 9.5 percent of deaths in the US from cancer in 2009. Stem cell transplantation, which aims to restore the function of the marrow, is an important therapy for these malignancies. Successful blood and marrow transplant requires the infusion of a sufficient number of hematopoietic stem and progenitor cells (HSPC), which is done by recruitment of HSPC from the marrow into the blood (mobilization). Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with chemotherapy. However, some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. Hence, improved methods to mobilize peripheral blood HSPC are warranted. The present invention is directed to novel short peptides of beta-defensins for improving the mobilization of HSPC.

Applications


  • Rapid and efficient mobilization of HSPC for clinical transplantation
  • Inhibition of malignant cell proliferation and metastasis

Advantages


·         Non-toxic, derived from a physiological molecule of innate host immunity

·         Cheap and simple synthesis

·         Rapid, robust and preferential mobilization of immature HSPC

·         Enhancement of mobilizing efficiency of presently used substances (e.g. G-CSF)

·         Dual use of the derivatives


Technology's Essence


Beta-defensins belong to a family of antimicrobial peptides, a major component of the innate immune system. In a mouse model, two different linear beta-defensin-derived peptides provided a strong and rapid HSPC mobilization, alone and in combination with G-CSF, a cytokine that is the major agent inducing robust mobilization of HSPC. In addition, a cyclic peptide derivative effectively inhibited HSPC mobilization and proliferation, as well as human malignant cell motility in mice. These findings make beta-defensin-derived peptides as promising small molecule candidates for improving current clinical HSPC mobilization protocols, and their cyclic derivatives as promising candidates for reducing cancer cell development and metastasis in patients.

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  • Prof. Tsvee Lapidot
1378
Researchers at the Weizmann Institute developed a novel method to design error-free DNA libraries from error-prone oligonucleotides. The system surpasses existing methods for de novo synthesis of DNA libraries in speed, precision, amenability to automation and ease of combining synthetic with natural...

Researchers at the Weizmann Institute developed a novel method to design error-free DNA libraries from error-prone oligonucleotides. The system surpasses existing methods for de novo synthesis of DNA libraries in speed, precision, amenability to automation and ease of combining synthetic with natural DNA fragments. 

All DNA construction protocols struggle with the cumbersome task of cloning and sequencing synthetic DNA fragments, seeking an error-free one. The problem is worsened for longer synthetic DNA which is more prone to errors. Time spent on error correction, clone selection and sequencing is a major bottleneck that prevents de novo DNA synthesis from becoming a routine procedure in labs. 

This innovative solution significantly decreases the need for labor-intensive time-consuming error correction methods, cloning and sequencing. Furthermore, efficient editing and reassembly of different genes is made possible due to a smart recursive reconstruction process.

 

Applications


  • Design and construction of synthetic biological molecules and organisms.
  • Construction of designer DNA libraries.

 


Advantages


  • Applicable in any lab with standard lab equipment. Faster and more precise than existing methods.
  • Amenable to automation, full synthesis in vitro with a modified smPCR protocol.
  • Very simple to combine synthetic and natural DNA fragments.
  • Does not require additional or external methods or reagents for error correction

 


Technology's Essence


Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed.

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  • Prof. Ehud Y. Shapiro
1407
Thermotolerant photosynthetic organisms endure worsening climate conditions such as increased temperatures and higher levels of CO2. These novel organisms maintain photosynthetic activity and growth under a wide temperature range (15-45oC) as opposed to their wild-type counterparts. Thermotolerant...

Thermotolerant photosynthetic organisms endure worsening climate conditions such as increased temperatures and higher levels of CO2. These novel organisms maintain photosynthetic activity and growth under a wide temperature range (15-45oC) as opposed to their wild-type counterparts.

Thermotolerant organisms also exhibit higher transparency to light. Photosynthetic efficiency is maintained even though they produce and utilize less chlorophyll molecules; therefore less surface area is required for optimal cultivation. Furthermore, increased CO2 concentrations are preferable for thermotolerant organisms’ efficient photosynthesis.

The innovative solution discovered at The Weizmann Institute, involves replacement of 1-2 amino acid residues in a protein motif within the D1 protein subunit of Photosystem II (the protein complex responsible for the conversion of solar energy to a useful form of energy by photosynthesis). Such a solution has the potential to provide platforms for food production and sustainable energy in regions with harsh climate conditions that until today, were deemed unfit for cultivation.

Applications


  • Bacterial platform to produce biomass or materials (e.g. nutraceuticals) in higher temperatures and higher CO2.
  • Food and biofuel production: adaptation of crops to harsh climates.

Advantages


  • Enhanced Thermal stability and plasticity of the modified organisms to a much broader range than observed for the native organisms.
  • Greater Light penetration (e.g. in ponds) without losing photosynthetic efficiency - thermotolerant organisms maintain efficient activity with less chlorophylls thus allowing greater transmission of light to deeper spaces.
  • Thermotolerant organisms withstand high CO2 concentrations.

Technology's Essence


Professor Avigdor Scherz and his team focused on the sequences of the two major protein subunits D1 and D2 found in all purple bacteria PSII reaction centers. Two sites, D1-209 and D1-212, were found to show consistent changes between mesophilic, thermotolerant and thermophilic organisms including cyanobacteria, algae and green plants.

The sites are positioned in a GXXXG-like structural motif (where G denotes small residues such as Gly, Ala, Ser, Cys and Thr) typical of helix-helix interactions. The motif was found at the points of closest contact between the two major protein subunits, D1 and D2. It was shown that mutations in the amino acids within the identified GXXXG-like motif  result in modification of the local flexibility of the reaction center and, consequently, in the induction of thermophilic behavior.

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  • Prof. Avigdor Scherz
1451
A monoclonal antibody against GluR3B, a peptide found in epilepsy patients, and especially in patients suffering from intractable, resistant forms of the disease, could be used in diagnosis kits as well as in drug development for this form of "autoimmune epilepsy".

A monoclonal antibody against GluR3B, a peptide found in epilepsy patients, and especially in patients suffering from intractable, resistant forms of the disease, could be used in diagnosis kits as well as in drug development for this form of "autoimmune epilepsy".

Applications


1. Producing a new kit for epilepsy patients, able to detect GluR3b Ab's and thus GluR3-mediated neuropathology
The anti GluR3B monoclonal Ab could be used for developing a new diagnostic kit to detect neuropathogenic human anti-GluR3B in serum and CSF of patients with epilepsy. The patient's GluR3B Ab's would compete and displace the GluR3B mAb's of its ligand: the GluR3B peptide. The presence of GluR3B Ab's in a patient, would indicate that autoimmunity against GluR3 may underlie the patient's neuropathology and a) would suggest the initiation of an immune-based therapy b) prevent useless and dangerous brain surgery c) prevent non-effective medication.

2. Drug design for GluR3-mediated neuropathology
The unique GluR3B monoclonal antibody could be used to screen a potential drug for 'Autoimmune Epilepsy'. The GluR3B monoclonal antibody could be used to screen for a molecule (i.e. Anti-idiotypic antibodies) that would block the GluR3 autoantibodies and their detrimental neuropathological effects.

3. Research tool for a kaleidoscope of purposes, including:

  • Detection of the GluR3 glutamate receptor subtype on various target cells.
  • Studies of the properties of the Glutamate/AMPA receptor subtype 3.
  • Studies of the Glutamate-liked agonist activity of the GluR3B monoclonal antibody, and of the GluR3 receptor ion channel gating properties.
  • Production of an animal model of 'Autoimmune Epilepsy'.
  • Studies of neuronal death caused by binding of the GluR3 autoantibody to glutamate/AMPA receptors.
  • Studies of behavioral impairments caused by binding of the GluR3 autoantibody to glutamate/AMPA receptors.

  • Technology's Essence


    Scientists from the Weizmann Institute of Science have discovered a unique anti-GluR3B monoclonal antibody Glu149/29/61.

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    • Prof. Vivian I. Teichberg
    • Prof. Vivian I. Teichberg
    1033
    A novel diagnostic test to identify individuals with increased risk of lung cancer. Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the...

    A novel diagnostic test to identify individuals with increased risk of lung cancer.

    Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the National Lung Cancer Trial (NLST) showed that early detection of lung cancer by low-dose CT reduces mortality by at least 20%. Despite recommendations for low-dose CT screening for heavy smokers fulfilling the NLST criteria, compliance is low. In addition, 80 million smokers and ex-smokers in the US who do not fulfil NLST risk criteria have no recommended solution.

    The MyRepair test fulfils this unmet medical need by providing a quantitative prediction of lung cancer risk using a simple blood test. The test is based on a personalized measurement of the patient’s DNA repair capacity, a mechanism which is highly connected to the onset of cancer. Therefore, the MyRepair technology can potentially increase early detection of lung cancer and thus save lives.

     

    Applications


    A novel diagnostic test to identify individuals with increased risk of lung cancer


    Advantages


    ·         Simplicity – MyRepair is based on a simple, cost-effective blood test.

    ·         Accessibility – Compared to low-dose CT which requires specific equipment, the MyRepair test can be easily integrated in general diagnostic labs and therefore may be more accessible to a larger portion of the population.

    ·         Additional applications – Since the test is based on measuring personalized DNA repair mechanism, it can be adopted in the future for the diagnosis of additional cancer types and DNA repair related diseases.


    Technology's Essence


    Based on the strong and well documented connection between impaired capacity for DNA repair and onset of cancer, the Livneh lab invented the MyRepair Test, a method for predicting lung cancer risk, based on measuring activity of 3 DNA repair enzymes.

    Combining enzyme activities with experimental risk estimates generated MyRepair Score, which measures personalized DNA repair capacity of tested subjects.

    An epidemiological/clinical study performed in Israel, further validated in an independent UK study, demonstrated that lung cancer patients have lower MyRepair Score than healthy people. In addition, subjects who test MyRepair-positive have an 85-fold higher risk to develop lung cancer compared to the general population.

    Low MyRepair Score is a risk factor independent of smoking, and of comparable magnitude, indicating that it can be a prognostic tool for smokers, ex-smokers, and non-smokers.

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    • Prof. Zvi Livneh
    1518
    Improved immunotherapy for breast cancer. Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of...

    Improved immunotherapy for breast cancer.

    Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of therapeutic mAbs and the evolution of patient resistance call for improvements. Furthermore, the response to the clinically approved monotherapy of Herceptin (a humanized mAb directed against ErbB-2), is relatively low (~15%) and short lived (median duration, 9 months). Therefore, there is a need to improve the therapeutic treatment against this receptor. The present technology enhances the therapeutic activity of anti-ErB-2 receptor antibodies, by combining two or more epitope-distinct antibodies.

    Applications


    • Improved treatment of ErbB-2-overexpressing tumors (e.g. in breast and ovary cancers).


    Advantages


    • May enhance patient response and delay acquisition of resistance.
    • Enhancement of therapeutic efficacy and synergy with chemotherapy.

    Technology's Essence


    Optimal selection of mAbs for cancer immunotherapy may improve its therapeutic potential. The outlined technology addresses an emerging strategy, which enhances the therapeutic activity of anti-receptor antibodies by combining two mAbs engaging distinct epitopes. It was demonstrated that pairs of anti-ErbB-2 mAbs better inhibit ErbB-2-overexpressing tumors than the respective individual mAbs, both in vitro and in vivo.

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    • Prof. Yosef Yarden

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