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Scientist
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
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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  • Dr. Karina Yaniv
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. Lea Eisenbach
1593
The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders.  To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools...

The study of social behavior in groups of mice may have crucial implications for understanding the social aspects of different disorders. 
To be executed correctly, group studies require the ability to track individual’s behavior within the group structure. The main challenge of current research tools is to allow individuals identification while maintaining sufficient resolution for accurate tracking.
The present technology provides a system that utilizes fluorescent fur dyes to differentially mark and track individuals within a group. Using a sensitive color camera and a newly designed tracking algorithm, behavior of groups may be recorded and analyzed with high temporal and spatial resolution.   
The technology further offers a method for characterizing the group’s interactions using the maximum entropy model.

 

Applications


 


Advantages


  • High spatial and temporal resolution – enabled by sensitive color video tracking.
  • Enables high detailed analysis of individual behavior within the group.
  • Suitable for community study of groups - limited only by available fur dyes.
  • Compatible with long-term analysis.
  • Simple, cost effective.
  • Minimal suffering and improved animal welfare.

  • Technology's Essence


    The present technology takes advantage of the fact that mice are nocturnal (active at night) animals, to mark their fur with different fluorescent dyes. Under ultraviolet light, the mice can be accurately and automatically tracked, over a number of days. As the mice are allowed to move freely in an interesting arena for exploration containing ramps, nest boxes and barriers (Figure 1), their trajectory and behavior are recorded using a sensitive color camera.
    The system further includes an image processing module which analyses the recorded images, calculates a spatiotemporal model and the nature of social interactions between individuals.
    Combining detailed behavioral and genetic analysis ate the level of individuals, in association with group analysis, may enable the identification of genetic and neuronal correlates of complex social interactions. 

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    • Prof. Alon Chen
    1441
    New protein as a target to treat B cell-related cancer.Chronic lymphocytic leukemia (CLL), a malignant disease characterized by the accumulation of B lymphocytes in the blood, lymphoid organs, and bone marrow, is the second most common type of leukemia in adults, accounting for about 7,000 new cases of...

    New protein as a target to treat B cell-related cancer.
    Chronic lymphocytic leukemia (CLL), a malignant disease characterized by the accumulation of B lymphocytes in the blood, lymphoid organs, and bone marrow, is the second most common type of leukemia in adults, accounting for about 7,000 new cases of leukemia each year. Presently, there is no cure for CLL, and the overall goal of leukemia treatment is to bring about a remission. Therefore, identifying new proteins that may serve as a target for inducing cell death in the malignant cells is highly desirable. The present technology identifies a new regulator protein that is essential for the survival of CLL cells.

    Applications


    • Treatment of CLL, as well as other B cell-related cancers (e.g. gastric cancer and renal cell carcinoma), by blocking CD84 activity
    • Diagnosis of CLL

    Advantages


    • Very specific to malignant B cells
    • Diagnosis, and therefore treatment, can be made at early stages of the disease

     


    Technology's Essence


    B cells taken from CLL patients have a high level of the protein CD84. Stimulation of CD84 upregulates the survival of B-CLL. However, inhibition of CD84 activity with a blocking antibody downregulates the expression of another protein which controls B-CLL survival, thus inducing cell death. Therefore, the present invention reveals CD84 as a regulator of B-CLL survival

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    • Prof. Idit Shachar
    1499
    Bladder cancer is a common malignancy; it is the 4th most common cancer in males and the 9th in females.  The presenting symptom is usually blood in the urine, and diagnosis is currently based on cystoscopy, which is invasive, costly, painful and time consuming.  To date, no biomarker has been...

    Bladder cancer is a common malignancy; it is the 4th most common cancer in males and the 9th in females.  The presenting symptom is usually blood in the urine, and diagnosis is currently based on cystoscopy, which is invasive, costly, painful and time consuming.  To date, no biomarker has been identified in the urine that might be used for screening, staging, prognosis and monitoring treatment.  We now report that the amount of the 60 kDa heat shock protein (HSP60) in a subject’s urine is a biomarker for muscle invasion in patients with bladder cancer – stage T2 and higher.  Moreover, subjects with stage T1 disease can be stratified by their urine levels of HSP60 into a sub-group likely to progress into stage T2 or into a sub-group more likely to respond to conservative treatment with BCG, which does not require removal of the bladder.  The distinction between these two sub-groups of T1 bladder cancer can identify earlier subjects in need of cystectomy, while sparing others unnecessary major surgery.

    Applications


    • Screening subjects with overt hematuria, or at risk of developing bladder cancer (such as heavy smokers)
    • tratifying bladder cancer subjects
    • Prognosis
    • Determining treatment program
    • Monitoring response to therapy.

    Advantages


    • Non-invasive
    • Easy to apply
    • Relatively inexpensive
    • Prognositic.

    Technology's Essence


    Quantitative measurement of HSP60 levels in a subject’s urine by ELISA, radio-immunoassay or other simple assays.

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    • Prof. Irun R. Cohen
    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

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