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Scientist
1671
A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined...

A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined conditions required for derivation and long term maintenance of such cells, without genetic modification.
Human naive pluripotent cells can be robustly derived either from already established conventional hESC lines, through iPSC reprogramming of somatic cells, or directly from ICM of human blastocysts. The new human pluripotent state was isolated and characterized; it can open up new avenues for patient specific disease relevant research and the study of early human development.

Applications


  • Reprogramming kits - Somatic cells to iPSC at near 100% efficiency (7days), iPSC to fully naive state.

Advantages


  • Deterministic iPSC reprogramming with no genetic modification required.
  • Stable pluripotency, with low propensity for differentiation
  • Reagents available off-the-shelf.

Technology's Essence


Hallmark features of rodent naive pluripotency include driving Oct4expression by its distal enhancer, retaining a pre-inactivation state of X chromosome in female pluripotent cell lines amongst others. Naive mouse ESCs epigenetically drift towards a primed pluripotent state; while human embryonic stem cells (hESCs) share several molecular features with naive mESCs (e.g. expression of NANOG, PRDM14 and KLF4 naive pluripotency promoting factors), they also share a variety of epigenetic properties with primed murine Epiblast stem cells (mEpiSCs). These observations have raised the question of whether conventioal human ESCs and induced pluripotent stem cells (iPSCs) can be epigenetically reprogrammed into a different pluripotent state, extensively similar with rodent na?ve pluripotency. Researchers at the Weizmann Institute discovered that supplementation of certain chemically defined conditions, synergistically facilitates the isolation and maintenance of pluripotent stem cells that retain growth characteristics, molecular circuits, a chromatin landscape, and signaling pathway dependence that are highly similar to naive mESCs, and drastically distinct from conventional hESCs.

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  • Dr. Jacob (Yaqub) Hanna
1745
Cancer is a leading cause of death in the developed countries. It is a highly heterogeneous disease even among patients with the same type and grade of cancer. Thus, drug development for cancer is extremely challenging. However there are some consistencies; most tumor cells exhibit genomic instability...

Cancer is a leading cause of death in the developed countries. It is a highly heterogeneous disease even among patients with the same type and grade of cancer. Thus, drug development for cancer is extremely challenging. However there are some consistencies; most tumor cells exhibit genomic instability with an increased expression of oncogenes and inactivation of tumor suppressor genes.
P53 is a key tumor suppressor that is mutated in more than half of the human cancers. Over the years several mouse models were developed in order to study p53 mutations. Interestingly it has been shown that mice homozygous for mutant p53 are viable, and develop malignant tumors only in adulthood.
Prof. Rotter and her team revealed the mechanism by which embryos are protected from mutant p53-induced transformation. They found, using embryos stem cells (ESCs), that the conformation of mutant p53 in ESCs is stabilized to a WT conformation. They further identified the network of proteins that may shift p53 transformation to its WT form.
This technology presents methods (compositions and kits) of stabilizing mutant p53 in ESCs by interacting proteins, thus propose a novel cancer therapy.

Applications


  • Cancer

Advantages


  • Targeted for p53
  • Safe

Technology's Essence


The researchers  hypothesized that cellular factors in the pluripotent cells contribute the stabilization of the WT conformation of p53. They used a mass spectrometry (MS)-based interactome analysis to examind the interaction network of the different conformations of p53 in WT and Mut ESCs compared with somatic cells from the spleen. They immunoprecipitated WT and Mut conformation of p53 and used p53 KO cells as controls for background binding. Importantly, they identifies chromatic-specific proteomic network that is suggested to bind p53 and act as a stabilizer of Mut p53 into a WT conformation. This network (59 proteins) includes the CCT complex, USP7, Aurora kinase, Nedd4, and trim24. Interactions with this network enables the activation of WT activity of p53 and eliminates the gain-of function Mut activities, despite the p53 mutation.
Overall this is a proposed mechanism of rescuing ESCs cells from transformation which sets the basis for future p53-targeted cancer therapeutics. 

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  • Prof. Varda Rotter
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
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
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
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
    1641
    A novel RNA-seq method enables unbiased identification and characterization of cell populations from low-quantity samples (~1000 cells). Utilizing tag-free FACS sorting, researchers at the Weizmann Institute are able to create single cell cDNA libraries in under two hours and at a low cost. As...

    A novel RNA-seq method enables unbiased identification and characterization of cell populations from low-quantity samples (~1000 cells). Utilizing tag-free FACS sorting, researchers at the Weizmann Institute are able to create single cell cDNA libraries in under two hours and at a low cost.

    As personalized medicine requires analysis of minute RNA quantities from patients, there is a great need for unbiased and comprehensive analysis of cells’ transcriptome from low-quantity samples.  Attaining simultaneous observation on millions of cells in their native context is currently a laborious and expensive process. Therefore an unbiased functional characterization of In vivo cell populations is of great demand.

    The Researchers have successfully addressed this challenge in a top down fashion by focusing on cell types. Using broad sampling of single cell transcriptional states from multi-cellular tissues they could reconstruct biological functions. They suggest a straightforward path to construct an unbiased map of functional cell states that are sampled directly from their native context. Thus they reveal a new methodology for microscopic analysis of the transcriptome in heterogeneous tissues.

    Applications


    The innovative technology has potential applications in basic research, personalized medicine and clinical diagnostics -

    ·         Kits for single cell transcriptome analysis of FACS output.


    Advantages


    ·         Dramatic reduction is costs and labor.

    ·         High resolution, robust.

    ·         Top down, unbiased.

    ·         No need to use markers.


    Technology's Essence


    This technology combines an automated 384-well cell capture and library preparation assay, two-tier molecular and cellular labeling and efficient poly-A tailed RNA conversion.  Amplification and sequencing of multiplexed libraries is achieved with 1000 cells in a single experiment.  Notably, each read in this method is directly interpretable as representation of a single RNA molecule from a specific single cell. The result is highly practical profiling of large cells samples. This further enables robust characterization of subpopulations’ functional state (at a resolution of 10 cells or 1% of 1000 cells sample).

    Moreover the researchers have developed a computational framework that aggressively filters noise and potential biases in the data using randomized molecular labels (RMT) and controls for different sources of amplification and inter-cell contamination errors.
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    • Prof. Ido Amit
    • Prof. Ido Amit
    1618
    A novel method is disclosed here for boosting the immune response, useful not only for the treatment of microbial and chronic viral infections, but also for activating the immune system against cancer cells. TLR-4 is a central player in the innate immune system as it specifically recognizes...

    A novel method is disclosed here for boosting the immune response, useful not only for the treatment of microbial and chronic viral infections, but also for activating the immune system against cancer cells. TLR-4 is a central player in the innate immune system as it specifically recognizes lipopolysaccharide (LPS), the major cell wall component of Gram-negative bacteria, and activates the immune system. Newly developed peptides derived from the N-terminus of a TLR-4 trans-membrane domain are capable of activating TLR-4 mediated immune response, thus useful both as stand-alone treatments and as vaccine adjuvants, increasing the immunogenicity of an antigen in a vaccine. Taken together, the newly developed peptides are useful for the treatment and prevention of a large variety of infections, such as microbial (e.g. Salmonella, Escherichia, Pseudomonas), viral (including HIV, Hepatitis and Influenza) and fungal infections. Further, they are useful in the treatment and prevention of a wide variety of cancers.

    Applications


    • Treatment for a wide variety of infectious diseases and cancers.
    • Prophylaxis for a wide variety of infectious diseases and cancers, as an adjuvant administered together with specific antigen.

    Advantages


    • Treats a wide variety of bacterial, viral and fungal infections.
    • Suitable both as a treatment and prophylaxis.
    • Boosts the endogenous immune system
    • Peptides are easy to synthetize and purify
    • Patient-friendly administration, either systemic or local.

    Technology's Essence


    The technology is based on the discovery that peptides derived from the N-terminus of a TLR-4 TM domain or their analogs are capable of activating TLR-4 mediated immune response. These peptides activate TLR-4 receptor, possibly by dimerizing within the cell membrane and stabilizing the TLR-4 dimer. Through TLR-4 activation, these peptides activate macrophages to secrete TNF-alpha, thereby stimulating the immune system. In addition, the ability of these peptides to modulate the immune system's innate response renders them useful as vaccine adjuvants, increasing the immunogenicity of an antigen in a vaccine.

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    • Prof. Yechiel Shai
    1555
    Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for...

    Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for designing an approach to protract the action in vivo of, potentially, any short-lived peptide/protein drug. In doing so two principal obstacles must be overcome: (1) following its conjugation, the probe introduced into a peptide or a protein should have sufficient affinity to albumin to manifest prolonged action in vivo, and (2) in case such covalent introduction results in an inactive product, the latter should be capable to undergo slow reactivation at physiological conditions. The present invention relates to engineering prolonged-acting prodrugs employing an albumin-binding probe that undergoes slow hydrolysis at physiological conditions.

    Applications


    • Prolonging half life of short-lined drugs

    Advantages


    • Prolonging the action of the drug without effecting its activity 
    • A desirable pharmacokinetic pattern

    Technology's Essence


    Since albumin is long-lived in vivo, drugs and endogenous substances that tightly associate with it have lower clearance rates than that of the unbound substances, and exhibit prolonged lifetime profiles in vivo. The present invention is based on a concept according to which a long chain fatty acid (LCFA) like albuminbinding compound is covalently linked to a short-lived amino-containing drug to form a non-covalent drug conjugate capable of associating with albumin in vivo, i.e., a long-lived prodrug that gradually releases the pharmacologically active constituent. This approach has been successfully implemented with several drugs (e.g. insulin, exendin and gentamicin).

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    • Prof. Matityahu Fridkin
    • Prof. Yoram Shechter

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