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1692
Novel immunosupressive peptides, derived from the TM domain of the HIV protein gp41, with high selectivity towards distinct immune cell populations.Uncontrolled activity of immune cells is an underlying cause of both autoimmune and inflammatory diseases. One of the major challenges in the field is to...

Novel immunosupressive peptides, derived from the TM domain of the HIV protein gp41, with high selectivity towards distinct immune cell populations.
Uncontrolled activity of immune cells is an underlying cause of both autoimmune and inflammatory diseases. One of the major challenges in the field is to develop therapeutics that would target specific populations of immune cells, in order to avoid immune-deficiencies that would leave patients exposed to infections.
The present invention provides novel peptides, based on Immunosupressive regions within the TM domain of the HIV gp41 fusion protein. These peptides were shown to specifically and efficiently inhibit T-cells and TNF? secretion from inflammatory macrophages. Importantly, these peptides were shown to have particular inhibitory effects towards T cells that are activated in a multiple sclerosis model. 

Applications


  • Selective therapy towards T cell mediated autoimmune diseases (e.g. multiple sclerosis)
  • Selective therapy towards TNF?-associated inflammatory disorders

Advantages


  • Specific towards defined cell populations – avoids general immune suppression
  • Significant efficiency towards MS-associated T-cell activation 

Technology's Essence


The present invention takes advantage of the potent immune evasion mechanisms that are utilized as part of the HIV virus pathogenesis. Gp41, a component of the virus envelop, is a transmembrane glycoprotein that mediates viral entry into cells of the immune system. In addition to its role in mediating the actual fusion event, gp41 has been shown to contain immunosuppressive activities that are attributed to its N terminus.
Using biochemical and biophysical approaches, Prof. Shai and his team from the Weizmann institute, reveal yet another immunosuppressive activity of gp41, exerted via its transmembrane domain. Importantly, this immunosupressive activity was shown to be specific for T cell activation (mediated through binding to CD3/TCR complex) and Toll-Like Receptor (TLR)-mediated activation of macrophages.
The present inventors generated synthetic peptides that derive from the gp41 trasmembrane domain and demonstrated their suppressive activity in both in-vitro and in-vivo models.
Significantly, T-cell activation was inhibited following activation with a peptide associated with the propagation of multiple sclerosis (MOG 35-55), proposing a specific inhibitory activity towards MS-generating mechanisms. Macrophages inhibition was shown to significantly compromise the secretion of pro-inflammatory factors, predominantly TNF?, following LTA (lipotechoic acid) activation. 

 

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  • Prof. Yechiel Shai
  • Prof. Yechiel Shai
1765
A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron.  Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns....

A new image reconstruction tool based on non-iterative phase information retrieval from a single diffraction pattern was developed by the group of Prof. Oron. 
Lensless imaging techniques enable indirect high resolution observation of objects by measuring the intensity of their diffraction patterns. These techniques utilize radiation in the X-ray regime to image non-periodic objects in sizes that prohibit the use of larger wavelengths. However, retrieving the phase information of the diffraction pattern is not a trivial task, as current methods are divided based on a tradeoff between experimental complexity and computational reconstruction efficiency.
The method described here is suitable for use with existing lensless imaging techniques to provide direct, robust and efficient phase data while requiring reduced computational and experimental complexity. This method, demonstrated in a laboratory setup on 2D objects, is also applicable in 1D. It can be applied to various phase retrieval applications such as coherent diffractive imaging and ultrashort pulse reconstruction

Applications


  • Phase microscopy
  • Signal processing
  • Holography
  • X-ray imaging

Advantages


  • A Generic solution to the phase retrieval problem
  • Non-iterative approach
  • An efficient and noise robust tool

Technology's Essence


The method is based on the fact that the Fourier transform of the diffraction intensity measurement is the autocorrelation of the object. The autocorrelation and cross-correlations of two sufficiently separated objects are spatially distinct. Based on this, the method consists of three main steps: (a) The sum of the objects’ autocorrelations, as well as their cross-correlation, are reconstructed from the Fourier transform of the measured diffraction pattern. (b) The individual objects’ autocorrelations are reconstructed from their sum and the cross-correlation. (c) Using the two intensities and the interference cross term, double-blind Fourier holograph is applied to recover the phase by solving a set of linear equations.

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  • Prof. Dan Oron
1670
A method for selective extraction of precious and rare metals has been developed at the Weizmann Institute. This method allows the efficient and environmentally benign recovery of precious materials that are currently discarded of in large quantities from spent catalysts (automotive and industrial)...

A method for selective extraction of precious and rare metals has been developed at the Weizmann Institute. This method allows the efficient and environmentally benign recovery of precious materials that are currently discarded of in large quantities from spent catalysts (automotive and industrial) from industrial processes (particularly in the electronic industry).

Prof. Igor Lubomirsky’s novel process is based on volatilization for selective extraction of precious and rare metals using benign metal salts, rather than dangerous chlorine gas as a chlorinating agent. The new process requires relatively low temperatures and is free from hazardous waste, among its additional advantages over conventional methods.

We believe that this efficient technology is key to increased reclaimed precious metals output, potentially resulting in the reduction of the demand for primary rare metals.

Applications


·           Recycling precious metals from spent items, e.g. platinum group metals from catalytic convertors


Advantages


·         No toxic input – chlorides are used rather than chlorine gas.

·         No hazardous waste is generated in the process.

·         Mild conditions. High-temperature furnaces and equipment are not required.

·         Relatively simple setup in comparison to conventional ones.

·         Small scale plants are economically viable.


Technology's Essence


Prof. Igor Lubomirsky and his group developed a novel method for the recovery of PGM from spent catalysts that can be applicable for other spent systems as well.

The method comprises of crushing the spent catalyst to obtain a catalyst particulate material with g a predetermined grain size and reacting it with chlorine containing salts rather than pure chlorine gas in a furnace at relatively low temperatures (900oC, far below the temperature required in the conventional volatilization method). This is followed by cooling the volatile PMG chloride product converting it into solid phase metal.

 

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  • Prof. Igor Lubomirsky
  • Prof. Igor Lubomirsky
1733
The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change...

The spatial distribution of proteins inside the cell is under tight regulation. This regulation is necessary to ensure proper functioning of the cell, and is of particular importance when extracellular stimulation is applied. Upon stimulation, many signaling proteins rapidly and dynamically change their location. Today, there is a widely recognized need to identify novel sequences which regulates nuclear translocation.
Recently, Prof. Zeger and his team discovered a new level of regulation to stimulated transcription. They showed that ?-like importunes are central mediators of nuclear translocation of signaling proteins. Furthermore they identified the site of interaction and designed accordingly a peptide which was found to prevent nuclear translocation.
This technology presents peptides with the potential of treating inflammatory and immune disease by regulating (prevent or promote) the translocation of proteins into the nucleus.

Applications


  • Inflammation
  • Immune diseases

Advantages


  • Effective
  • Safe

Technology's Essence


The researchers found that ?-like importins play a key role in JNK and p38 translocation. They also found that the translocation of these MAPKs is mediated by the formation of either Imp3/Imp7/MAPK or Imp3/Imp9MAPK heterodimers. Most importantly, the researchers identified the site in p38 that mediate the interaction with Imp7 and Imp9 and showed that the important sequence lies within residues 20-30 of p38?. Subsequently they synthesized a 14 amino acid myristoylated peptide based on the sequence of residues 21-34 of p38?. When it was applied to HeLa cells prior to stimulation, it prevented the nuclear translocation and Imp7/9 interaction of the MAPKs. Since the peptides of this technology are able to specifically inhibit the nuclear activities of p38 (such as inflammatory activities) without modulating their cytoplasmic activities, these peptides may serve as a therapeutic agent for inflammatory and apoptosis related diseases without having side effect.

 

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  • Prof. Rony Seger
1646
Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series...

Dedicated and highly efficient EPR analysis of small volume samples in a range of few µl is now made simple with a novel device invented at the Weizmann Institute of Science. This device features a new ejection mechanism and a unique cold trap which enables collection of all time points in a RFQ series in one continuous experiment.
In order to design and develop inhibitors for therapeutic purposes, the reaction mechanisms of enzymes must be understood. For biological applications, a common methodology of addressing this need is combining Rapid Freeze Quench with Electron Paramagnetic Resonance (RFQ)-EPR, which allows the trapping and analysis of short lived intermediates in chemical reactions. However, commercial RFQ-EPR devices are limited for high field EPR applications due to the demand of large sample volumes for each time point.
Prof. Goldfarb and her team built a new RFQ apparatus based on microfluidic flow and unique ejection and freezing systems, which can be used for collecting small volume samples in capillaries for high field EPR.

Applications


This technology, combined with the variety of W-band high resolution EPR technique (ENDOR, DEER and ESEEM) enables better mechanistic studies of enzymatic reactions, with an emphasis on structural transformations during the reaction, in an efficient and accurate way.


Advantages


  • Collecting all RFQ time points in one continues experiment.
  • Produce small volume samples in the range of a few µl, and handles small capillaries, for high field ERP.
  • An improved dead time of ~5ms, relative to the commercial RFQs with a typical dead-time of 5–10 ms.
  • Ease-of-use and speed.

Technology's Essence


The innovative apparatus consists of two main parts: the microfluidic device and the freeze-quench setup. The microfluidic device comprises a mixer, which mixes the two reacting solutions, a flow path where the reaction occurs, and a sprinkler from which the solution is sprayed out of the device. Prof. Goldfarb and her colleagues improved the common mixing device by adding a fast stream of nitrogen gas which mixes with the ejected reaction solution, and sprays the frozen aerosol out in tiny drops at high speed.
The innovative RFQ device was planned to have a cold solid surface on which the freezing happens rather than the traditional ejection into a cold liquid, in order to minimize the losses of the frozen solution. Moreover the plate rotates at a speed correlated to the flow speed of the solution, thus samples of different reaction times can freeze on a different radius. The frozen samples are then collected into quartz capillaries.

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

A potent combination therapy against non-invasive breast cancer

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

 

Applications


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

 


Advantages


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

 


Technology's Essence


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

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

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

Applications


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

Advantages


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

Technology's Essence


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

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  • Prof. Irit Sagi
1583
The thermoelectric effect is the direct conversion of temperature differences to electric voltage and vice versa. Thermoelectric effects are used in various applications, where heat energy is saved, that would be otherwise lost. Although the TE conversion efficiency is nowadays low (5-8%), the novel...

The thermoelectric effect is the direct conversion of temperature differences to electric voltage and vice versa. Thermoelectric effects are used in various applications, where heat energy is saved, that would be otherwise lost. Although the TE conversion efficiency is nowadays low (5-8%), the novel technique developed at Weizmann Institute, has a disruptive potential to change this market.  

Prof. Y. Imry and his team at Weizmann Institute came up with Thermal Electric conversion technique, based on a new TE device architecture which allows performance enhancement. The core invention is in the field of Bi-junction thermoelectric device architecture, having a thermoelectric gate interposed between two electric regions, leading to thermal electric conversion efficiency optimization.

Applications


Various TE devices will benefit from better TE efficiency, achieved by the developed conversion technique. The growing market for thermoelectric energy harvesters will reach $865 million by 2023. Current TE market is driven by consumer energy harvesting applications and some niche segments:

  •  Automotive energy harvesting applications, since around 40% of the energy produced by internal combustion engines is currently lost in heat through the exhaust.
  • Wireless devices/sensors segment is forecasted to account for over a third of the overall market for thermoelectric harvesters and cooling by 2023.

Advantages


In order to drive down the thermoelectric module costs and facilitate broad deployment, TE has several barriers to overcome: 

  •  low conversion efficiency;
  • toxicity and low availability of chemical elements constituting part of the thermoelectric materials.

 In this context, the main TE market challenges are reaching higher efficiencies using low cost thermoelectric materials. These challenges can be addressed by the proposed technology.


Technology's Essence


Prof. Y. Imry and his team at Weizmann Institute have developed novel bi-junction TE device, having a thermoelectric gate interposed between two electric regions, aiming at TE efficiency improvement. Thermoelectric efficiency depends on the figure of merit (ZT). The figure-of-merit curves, for the developed 3-T TE device configurations show that higher ZT should be achieved.  

The secret essence of the invented configuration is in using two independently adjustable input parameters - voltage and temperature - as drivers for optimizing device thermoelectric efficiency.

 

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  • Prof. Yoseph Imry
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
1554
We present a novel approach resulting in efficient and robust wireless energy transfer in the mid-range. Applications of wireless energy transfer are already in use and are continuously being developed. The main limit of wireless energy transfer techniques is that both the transmitter and transformer...

We present a novel approach resulting in efficient and robust wireless energy transfer in the mid-range. Applications of wireless energy transfer are already in use and are continuously being developed. The main limit of wireless energy transfer techniques is that both the transmitter and transformer need to be of the same resonance. In addition, this technique is very susceptible to noise which limits efficiency. The present invention provides a technique for a robust and efficient mid-range wireless power transfer between two coils. This technique can transfer the energy between the coils without being sensitive to any resonant constrains, noise and other interferences that exist in the neighborhood of the coils

Applications


  • Simultaneous energy transfer to several electrical gadgets.

Advantages


  • Efficient
  • Not sensitive to electrical interference.
  • No need for an exact resonance match between transmitter and transformer.

Technology's Essence


The efficiency and robustness of this technology is achieved by adapting the process of rapid adiabatic passage (RAP) for a coherently driven two state atom to the field of wireless energy transfer. In other words, the resonance of the transmitter is tuned adiabatically to scan a resonant frequency range, thus arriving at a dynamic solution to the electrical transfer problem.

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  • Prof. Yaron Silberberg
1604
Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic...

Novel reporter gene for magnetic resonance imaging applications.The ability to image the duration and location of gene expression in vivo and noninvasively is imperative for the future of biology and clinical medicine. Magnetic Resonance Imaging (MRI) is a widely used noninvasive clinical diagnostic tool that offers views into deep tissues at exquisite spatial resolution. Recently, MRI has emerged as a valuable tool for monitoring the expression of genes by utilizing metal-complexed MRI agents to display transgene activity in vivo. However, administration of metal complexes into tissues and cells is challenging. Intra-cellular metalloproteins such as Ferritin have been utilized as endogenous MRI contrast agents, but offer relatively low sensitivity. The present technology provides a novel Ferritin-based transgene with enhanced MRI contrast.

 

Applications


  • Non-invasive imaging of gene expression in transgenic mice models.
  • Monitoring target gene expression in pre-clinical studies.
  • Long-term cell labeling and tracking.
  • Visualization of cellular- and gene-based therapeutics.

Advantages


  • Does not require delivery of exogenous substrate.
  • Enhanced MRI contrast over current Ferritin-based reporters.
  • Conversion to magnetite is achieved in physiological conditions and not by synthetic modification or by extreme heating. 

Technology's Essence


Ferritin, the main Iron storage intracellular protein, contains a paramagnetic ferryhydrate core, and thus was proposed as an endogenous MRI reporter gene. However, Ferritin provides relatively low sensitivity. One way to increase sensitivity of Ferritin is to convert the non-crystalline ferrihydrate in its core into crystal magnetite as has been done chemically, to form magneto-ferritin. The current method enhances the magnetic properties of Ferritin by engineering a Ferritin protein fused to a bacteria-derived peptide. This novel recombinant fusion protein facilitates conversion of ferrihydrate into crystal magnetite and by this induces MRI contrast. The new construct can serve for monitoring delivery and differentiation of cells in vivo in cellular based therapy. 

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

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

Applications


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

Advantages


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

Technology's Essence


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

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  • Prof. Yosef Yarden
  • Prof. Michael Sela
1587
An innovative technique to preserve and prolong shelf-life in crop-plants cost-effectively. Different agricultural crops from Solanaceous species which include tomato, potato and eggplant, overcome oxidative stress by the production of steroidal glycoalkaloids (SGAs) and steroidal saponins. Although...

An innovative technique to preserve and prolong shelf-life in crop-plants cost-effectively.
Different agricultural crops from Solanaceous species which include tomato, potato and eggplant, overcome oxidative stress by the production of steroidal glycoalkaloids (SGAs) and steroidal saponins. Although SGAs contribute to plant resistance to a wide range of pathogens and predators some are considered as toxic to humans, with potato known as most relevance to food safety.
This innovative technology offers improvement  of nutritional composition and prolonged shelf-life of Solanaceous species, which are widely consumed crop-plants with a market size of hundreds of billions of tones produced yearly worldwide.

Applications


Modification of steroidal glycoalkaloids and steroidal saponins compounds in plants can be used for two purposes:
1. Widely used crop-plants from Solanaceae species with reduced anti-nutritional components.  Leading to a longer shelf-life of crop-plants with safer nutritional compounds. 
2. Highly resistant modified plant with enriched toxic steroidal glycoalkaloids content for non-edible usage. 

Advantages


  • Prolongs shelf-life- by preventing post-harvest elevated toxicity levels.
  • Reduction of undesired anti-nutritional alkaloids, by means that do not affect other biological plant pathways.
  • Helps avoiding spoilage and toxicity of plants that manifest during storage and process.
  • Stress and pathogen-resistant plants for non-edible usage: Genetically modified plants with elevated toxic steroidal glycoalkaloids content will result in enhanced resistance to stress related factors. The outcome will also be prolonged shelf-life achieved in a clean economic manner (reduced need of pesticides/ insecticides).

Technology's Essence


The invention relates to key genes and enzymes on the biosynthesis pathway converting cholesterol to SGA. Biosynthesis involves an array of genes. Modulation of specific regulatory, transcription factor genes had enabled strict control of the production of steroidal alkaloids and glycosylated derivatives therefore.
Prof. Asaph Aharoni discovered the key genes in the biosynthesis of steroidal saponins and steroidal alkaloids in his lab at the Weizmann institute. He also developed a method for altering the gene expression and the production (reduction or elevation) of these components in plants from the Solanaceae species.

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  • Prof. Asaph Aharoni
1662
Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and...

Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and cancerous cells. Also, the therapeutic role of the immune system is an essential element in the healing process due to bone marrow transplantation for hematologic malignancies.
However, a more efficacious and less toxic T cells based treatment is required. Effective therapy depends on the functional avidity between T cell receptors (TCRs) and peptide-MHC complex (pMHC). However the natural affinity of TCR is low and they do not naturally undergo the processes that improve antibody affinity, such as somatic hypermutation (SHM). Currently there is no method of increasing the affinity of a TCR to its ligand. Moreover there is no knowledge on how use affinity maturated TCRs for creating anti-tumor reactive cells
This technology presents a method of increasing the affinity of a TCR to its ligand. This is done by subjecting TCR genes to SHM via the enzyme Activation Induced cytidine Deaminase (AID). The technology further provides affinity maturated TCRs (in cell- bound or in soluble form) and their pharmaceutical potential for immunotherapy. 

Applications


  • Generating anti-tumor T cells
  • Generating T cells reactive against selected antigen

Advantages


  • Rapid
  • Effective

Technology's Essence


This novel technology reveals that the affinity of a TCR to its ligand may be increased remarkably by subjecting TCR genes to SHM, directed by AID.
First a nucleic acid construct encoding a TCR gene is expressed in a host cell. Next SHM is used to introduce mutations to the TCR gene. Last, the the cells will be analyzed for affinity maturation by tetramer staining and subsequently sorted by FACS.
There are three parallel approaches to perform affinity maturation for the TCR: (1) Ex-vivo affinity maturation system, using Tet-regulated expression of AID (2) Ex-vivo affinity maturation system, using controlled expression of AID by mRNA electrophoresis (3) In-vitro affinity maturation system, using extracts from cells that are in SHM and recombinant AID.

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  • Prof. Rachel Lea Eisenbach

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