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Technology Name
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Scientist
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
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
    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
    1629
    A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.Nearly...

    A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.
    Nearly all methods analyze pathway activity in a global “atomistic” manner, based on an entire sample set, not attempting to characterize individual tumors. Other methods use detailed pathway activity mechanism information and other data that is unavailable in a vast majority of cancer datasets.
    The new algorithm described here transforms gene-level information into pathway- level information, generating a compact and biologically relevant representation of each sample. This can be used as an effective prognostic and predictive tool that helps healthcare providers to find optimal treatment strategies for cancer patients. Furthermore, this method can be generically used for reducing the degrees of freedom in order to derive meaningful output from multi-dimensional data using limited knowns.

    Applications


    • Personalized cancer treatment.
    • A tool for mining insight from large datasets with limited knowns.

    Advantages


    • Provides personalized solutions.
    • Can be utilized for rare conditions with very limited known information.
    • Proved on real oncologic datasets.
    • A Generic unsupervised learning tool.

    Technology's Essence


    The algorithm analyzes NP pathways, one at a time, assigning a score DP(i) to each sample i and pathway P, which estimates the extent to which the behavior of pathway P deviates from normal, in sample i. To determine this pathway deregulation score the expression levels of those dP genes that belong to P using available databases are used. Each sample i is a point in this dP dimensional space; the entire set of samples forms a cloud of points, and the “principal curve” that captures the variation of this cloud is calculated. Then each sample is projected onto this curve. The pathway deregulation score is defined as the distance DP(i), measured along the curve, of the projection of sample i, from the projection of the normal samples.

     

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

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

    Applications


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

    Advantages


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

    Technology's Essence


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

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

    Sphingolipid-peptide conjugates with potent anti-viral activity.

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

     

    Applications


    ·         Design of novel HIV therapeutics.

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

    ·         Topical blockers of viral transmission.

     


    Advantages


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

    Technology's Essence


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

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

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

     

    Applications


    Treatment of various T-cell mediated pathologies including:

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

     


    Advantages


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

    Technology's Essence


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

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    • Prof. Yechiel Shai
    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
    1397
    A novel antibody which can be used, for the first time, to recognize ubiquitinated histone 2B. This technology is novel in its ability to recognize proteins and their destinations, and may serve in diagnostics and immunoprecipitation processes.

    A novel antibody which can be used, for the first time, to recognize ubiquitinated histone 2B. This technology is novel in its ability to recognize proteins and their destinations, and may serve in diagnostics and immunoprecipitation processes.

    Applications


    Primary applications in research. Use as a detection tool in western blotting, immunoprecipitation and chromatin immunoprecipitation. Might be used for monitoring processes associated with modulations of ubiquitinated-H2B levels.

    Technology's Essence


    The invention involves the generation of antibodies specific to ubiquitinated-H2B which selectively recognize H2B when it is ubiquitinated but not H2B in its unmodified state, or ubiquitin unconjugated to H2B.

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    • Prof. Moshe Oren
    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
    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
    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
    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
    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

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