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Biotechnology, Pharma and Diagnostics

Category
Technology Name
Briefcase
Scientist
1871
As the world’s population grows, and climate changes, there is a strong need for breeding hardier crops in a precise fashion. The traditional method of introducing new traits to a plant via traditional breeding methods is a slow and stochastic process, which can require growing a large number of plants...

As the world’s population grows, and climate changes, there is a strong need for breeding hardier crops in a precise fashion. The traditional method of introducing new traits to a plant via traditional breeding methods is a slow and stochastic process, which can require growing a large number of plants to screen for desired progeny. Additionally, it can be difficult to generate a new variety with only the desired traits without any extra undesired traits being introduced in the process. The reason being is the randomness of genetic recombination during reproduction and due to the genetic linkage between desirable and undesirable traits. Therefore, it would be of great value to precisely shuffle genetic elements between chromosomes in both somatic and meiotic plant cells at specific sites.

The group of Prof. Avi Levy have recently devised a method for inducing site specific recombination between homologous chromosomes using CRISPR/Cas9. The technology has numerous applications including allelic replacement in somatic cells. As well as performing reciprocal exchanges of large homologous chromosomal segments at specific locations, enabling recombination events that are rare via traditional breeding. The technology also has great promise in relation to the regulatory environment; as the USDA has stated that it would not oversee multiple crops that were ‘gene edited’ by CRISPR/Cas9[1]. Consequently, this technology has great value as a method for combining specific crop traits and for improving the accuracy of plant breeding in plants.

 

Applications


?  Inducing targeted Homologous Recombination

?  Improving Plant Breeding – through a higher precision of the exchange of chromosomal segments and through the use of smaller populations

?  Applicable with any nuclease system – Simply requires that the system generates a DSB in somatic cells of a hybrid plant. (e.g. TALENs, CRISPR/Cas9, …)


Advantages


The research team led by Prof. Avi Levy at the Weizmann Institute of Science has developed a method to site specifically induce homologous recombination (HR) between chromosomes. The team has applied the innovation in tomato and in Arabidopsis plants. CRISPR/Cas9 was used to perform site specific double strand breaks (DSB) on homologous chromosomal sections. Then using a series of phenotypic and molecular assays, the Levy team could show the DSB repair events were due to HR (either crossover or non-crossover) rather than non-homologous end joining (NHEJ).

 

[1] With a free pass, CRISPR-edited plants reach market in record time. Nature Biotechnology 36, 6–7 (2018). https://www.nature.com/articles/nbt0118-6b

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  • Prof. Avraham A. Levy
1865
THE INNOVATION:   A non-chromatographic antibody purification method not relying on Protein A nor any ligand, had been developed. Highly pure (>95%) human, mouse, rabbit or sheep IgG's are obtained in good yields within 20-30 minutes. The technology addresses a projected $440M antibody purification...

THE INNOVATION:

 

A non-chromatographic antibody purification method not relying on Protein A nor any ligand, had been developed. Highly pure (>95%) human, mouse, rabbit or sheep IgG's are obtained in good yields within 20-30 minutes. The technology addresses a projected $440M antibody purification reagents market.

 

MARKET OPPORTUNITY:

 

The past two decades have evidenced a strong focus on monoclonal antibody (mAb) therapeutics. Today, there are already 50 antibody-based drugs on the market; more than 550 are at various stages of development; and the competition among the large biopharmaceutical companies is aggressive. The global market for mAb therapeutics in 2014 reached USD 80.3 billion. The global mAb market is expected to rise at a compound annual growth rate (CAGR) of 8.1% to nearly USD 128 billion by 2020. The development of these new molecular agents, successfully directed to specific cellular targets, is playing a crucial role in the pharmaceutical industry. This trend shows the strong focus of top biopharmaceutical companies on biologics, including mAb therapeutics (Frost & Sullivan 2015).

 

Accordingly, the rapid growth of the mAb market is driving pharmaceutical firms to find avenues that will reduce production costs. Purification of mAb's, is still a major contributor (50-80%) of manufacturing costs, particularly due to the use of Protein A columns. Whereas Protein A is the most efficient, specific and common ligand used by all biopharmaceutical companies, it is also highly expensive. It is estimated that removal of the Protein A step would cut 40% in the total production costs of mAb's and this is exactly what our technology is aiming at. 

 

THECHNOLOGY:

 

The technology relies on unique detergent scaffolds onto which IgG's bind almost quantitatively, whereas the vast majority of non-IgG proteins are rejected. Bound IgG's are recovered from the detergent scaffolds in great purity (>95%) while leaving residual impurities behind. IgG purification was demonstrated in serum-free media containing BSA\HSA. The fact that, purified IgG's preserve their binding specificity, implies that, the presented method may provide a cost-effective viable alternative to: Protein A chromatography 

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  • Prof. Mordechai Sheves
1770
Obesity is reaching epidemic proportions throughout the western world and is also now becoming a problem in a number of countries in the developing world. This is primarily due to the over-consumption of high-calorie foods compounded with the lethargic lifestyles that are becoming common place. The...

Obesity is reaching epidemic proportions throughout the western world and is also now becoming a problem in a number of countries in the developing world. This is primarily due to the over-consumption of high-calorie foods compounded with the lethargic lifestyles that are becoming common place.

The issue of obesity is that it is linked to the development of many other diseases such as diabetes, heart disease, and cancer. Consquently numerous countries healthcare systems are being put under enormous strain from the increase and severity of obesity related diseases. Additionally the financial strain is being compounded by the requirement for special equipment in hospitals that are larger and reinforced to handle the more extreme cases that are becoming common. Therefore there is a clear need for a treatment that can reduce obesity in a cost-effective manner and that is simple for individuals to follow.

The present technology from the laboratory of Prof. Yosef Shaul offers a novel target in reducing obesity by inhibiting c-Abl kinase, which has the added benefit of being a well-known and clinically tested drug target. Subsequently the technology offers a new method in reducing obesity using a well understood molecular target that has already been tested for other diseases. 

Applications


?  Generating therapeutics towards reducing obesity.


Advantages


·         Specific – the technology targets c-Abl kinase to reduce obesity.

·         Well Studied – c-Abl has been studied and targeted for other indications.

·         Clinically tested – small molecule c-Abl inhibitors such as Imantinib (Gleevec) have been clinically approved for treating cancer, possibly simplifying future clinical trials.

·         Numerous therapeutic options – A variety of small molecule inihibitors already exist along with other options such as RNAi to target c-Abl.


Technology's Essence


The invention is the inhibition of the Abelson murine leukemia viral oncogene homolog 1 (c-Abl) for the purpose of reducing obesity. The inhibition of the c-Abl kinase activity has the effect of lowering the amount of peroxisome proliferator-activator receptor gamma 2 (PPAR?2), which is known as a master regulator in the development of adipocytes (fat accumulating cells). The mechanism works by reducing the stability of the PPAR?2 and leading to its to depletion. Subsequently it has been shown that inhibiting c-Abl leads to reduced fat accumulation in cells and lowering of body mass in multiple mouse models.  

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  • Prof. Yosef Shaul
1762
Hair loss (alopecia) is mostly associated with aging, although it can affect people at various ages. Genetics, drugs, chemotherapy, stress, and medical conditions are just a few of the factors that are associated with alopecia. Non-surgical medical treatments for alopecia, such as oral and topical...

Hair loss (alopecia) is mostly associated with aging, although it can affect people at various ages. Genetics, drugs, chemotherapy, stress, and medical conditions are just a few of the factors that are associated with alopecia. Non-surgical medical treatments for alopecia, such as oral and topical drugs, may have severe side effects and are not always effective in restoring lost hair. Therefore there is a need for medications that can encourage hair growth as well as prevent further balding.

The team of Dr. Valery Krizhanovsky discovered that by eliminating senescent cells in the epidermis they can revive hair follicle stem cells that induce hair growth. The team achieved this via the use of small molecule inhibitors of Bcl-2 family proteins and showed that such treatment is beneficial to the viability of senescent cells in the epidermis, subsequently able to restore hair growth potential.

Advantages


?  Restores hair growth potential – induces repopulation of stem cells in follicles, possibly returning hair growth and preventing hair loss.

?  Wide variety – can be used to treat alopecia, whether due to genetic, environmental or behavioral factors, or following chemotherapy.

?  Non-androgenic – can be used by both men and women.


Technology's Essence


The group of Dr. Krizhanovsky showed that Bcl-W and Bcl-XL are elevated in senescent cells and provide the cells with resistance to apoptosis. Using a mouse model whereby epidermal senescent cells were induced, led to fur loss in the mice. The Krizhanovsky team then checked inhibition of Bcl-2 family proteins by relevant small molecule inhibitors, which induced proliferation of stem cells in the hair follicles restoring the capacity of hair growth. Furthermore the principle concept of the Krizhanovsky groups work has been corroborated independently. By using a fast-aging mouse model that has accelerated hair loss, the group of Dr. de Keizer demonstrated in vivo that inducing senescent cell apoptosis targeting a separate pathway, led to the restoration of fur growth[1]



[1] Baar et al., 2017, Cell 169, 132–147

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  • Prof. Valery Krizhanovsky
1810
Culturing and expanding T cells ex-vivo, while retaining their functionality, is an essential factor for the development of cutting-edge immunotherapies. A major problem frequently faced by physicians is the low number of T cells available for adoptive immunotherapy, and the difficulty to retain their...

Culturing and expanding T cells ex-vivo, while retaining their functionality, is an essential factor for the development of cutting-edge immunotherapies. A major problem frequently faced by physicians is the low number of T cells available for adoptive immunotherapy, and the difficulty to retain their functionality following extended incubation ex vivo. Specifically, cultivation of T-cells commonly leads to short term cell proliferation, which is followed by gradual loss of functionality, growth arrest, and increased cell death.  Consequently, there is a strong need for the development of novel technologies that could increase T-cell proliferation, while maintaining, or even enhancing their functionality.

The groups of Prof. Benjamin Geiger and Prof. Nir Friedman have identified unique conditions for inducing T cell proliferation ex vivo. The technology is based on supplementing factors to the media and affixing factors to the surface of the cell culture device. The conditions developed by the joint Geiger-Friedman team greatly enhanced the expansion of CD4+, CD8+, and additional types of T cells. Moreover, functional testing of specific cytotoxic T-lymphocytes demonstrated a remarkably-enhanced capacity of killing relevant cancer cells, both ex vivo and in vivo.

Applications


·         Expanding large quantities of CD4+ and CD8+ T cells ex-vivo, for example tumor infiltrating T cells (TILs) from biopsies.

·         Producing highly functional antigen-specific CD8+ T cells for tumor suppression.

·         Capacity to stimulate functional CAR-Ts and TILs.


Advantages


·        Simple – coating vessels with the particular T cell stimulatory factors that are commercially available.

·        Specific – Co-culturing with antigen loaded dendritic cells allows antigen-specific T cell expansion (e.g. cancer neo-antigen T cells). 

·        Compatible – stimulating CAR-T cells and possibly TILs.


Technology's Essence


The Geiger-Friedman team has discovered a novel set of conditions that induce the growth of T cells, using a specific combination of T cell stimulators attached firmly to the culture device along with soluble stimulatory cytokines. The team was able to effectively produce large numbers of T cells which retain full or even enhanced functionality, e.g. killing of specific cancer cells in culture and in vivo. 

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  • Prof. Benjamin Geiger
1776
A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient. Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the...

A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient.

Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the same since the 1970’s, involving systemic chemotherapy treatment, and surgery. The problem of limited treatment options is further exacerbated due to the high proportion of patients who relapse following chemotherapy.

The group of Prof. Yosef Yarden at the Weizmann Institute of Science (WIS) has discovered that amphiregulin (AREG) levels are elevated in the body fluids of a high percentage of ovarian cancer patient samples they tested. Prof. Yarden’s group has found that by intercepting AREG in combination with chemotherapy, they were able to inhibit the growth of ovarian tumors.

Applications


·         Inhibiting growth of ovarian cancer.

·         Possible treatment for other types of cancer.

·         Using AREG as a possible theranostic for ovarian cancer.


Advantages


·         Innovative Target – Intercepting the EGF-ligand AREG.

·         Flexible – Anti-AREG mAbs could be used alone or in combination with current chemotherapy treatments for different malignancies.


Technology's Essence


Prof. Yosef Yarden and his group have found that the EGFR ligand, Amphiregulin (AREG) was elevated in the bodily fluids of 80% of cancer patient samples tested. These results were further supported by in vitro work with varying cancer cell lines, again showing elevated AREG concentrations in their media. The Yarden group then generated an anti-AREG antibody, and performed experiments in vivo using mouse models xenografted with ovarian cancer cells. The results show that co-administering the anti-AREG antibody re-sensitized the tumors to standard chemotherapy treatments. This emphasizes the value of AREG not only as an anti-cancer target but also as a possible diagnostic marker.  

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  • Prof. Yosef Yarden
1774
A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies. Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect...

A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies.

Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect on this specific malignancy. The reason is that lung cancer cells regularly acquire resistance through multiple compensatory mechanisms, including secondary (new) mutations in receptors which block the effects of TKIs; up-regulation of specific genes; or rewiring of signaling networks.

The current technology works around these compensatory mechanisms by using a mixture of antibodies that function in a synergistic manner, to effectively and specifically target lung cancer cells, without affecting healthy cells.

Applications


·         Treatment of non-small cell lung cancer (NSCLC).

·         A method for augmenting currently available TKIs.


Advantages


·         Specificity – treatment was able to target EGFR-mutated NSCLC cancer cells, and showed no effect on healthy cells.

·         Effective – able to strongly inhibit NSCLC cancer cell lines and inhibit xenografted NSCLC cells in a mouse model.

·         Novel Approach – utilizing data derived from both clinical and laboratory research to devise a method for counteracting compensatory mechanisms of cancer cells.


Technology's Essence


Prof. Yosef Yarden and his group have discovered that by simultaneously inhibiting multiple receptors, namely HER2 and HER3 along with EGFR, they could effectively circumvent the compensatory mechanisms and inhibit NSCLC cell growth. This was determined using a combination of clinical, in vitro, and in vivo data. In addition, in vivo experimental work included xenograted mouse models where only the triple combination of antibodies effectively reduced tumor volume relative to standard mAb treatments.

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  • Prof. Yosef Yarden
1790
A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix. Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for...

A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix.

Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for vulnerable populations such as children and seniors. This is due to the host immune response which can damage the lung tissue, serving as a prime target for secondary infections. Consequently, there is a need for a method that provides better control over inflammatory response and reduces tissue damage caused by the host immune response to an infection.

Prof. Irit Sagi’s research team has discovered that by specifically inhibiting MT1-MMP they can limit tissue damage in the lungs of mice, help prevent secondary infections, and subsequently improve overall survival rates.  

Applications


·         Limiting tissue damage for the prevention and treatment of secondary infections.


Advantages


·        Novel mechanism – targeting MT1-MMP to limit inflammation due to an immune response, rather than targeting the pathogen directly.

·        Usage of an antibody for prophylaxis or treatment

·        Synergism – possibly combined with an anti-pathogen agent to assist in treatment. 

·        Better outcomes – reduction of tissue damage and inhibition of secondary infections improves overall survival rates.


Technology's Essence


The research team of Prof. Irit Sagi has shown a novel mechanism of treating and preventing secondary infections by inhibition of MT1-MMP using an anti-MT1-MMP antibody. The team used mice as an infection model. They performed in vitro experiments on extracted mice lungs to characterize MT1-MMP’s role in the infection pathology. They also calculated survival rates following both primary and secondary infections of mice, with and without inhibition of MT1-MMP. Which showed that the inclusion of the anti-MT1-MMP antibody improved overall survival rates in the infected mice.

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  • Prof. Irit Sagi
1760
Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with...

Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with issues of harsh side-effects of using said drugs.

Currently one of the most problematic antibiotic resistant bacterium is methicillin-resistant Staphylococcus aureus (MRSA). MRSA is becoming prevalent in hospitals and care homes, increasing the risk associated with hospitalization and invasive medical procedures. Therefore there is an urgent need to develop new antibiotics to combat MRSA.

The present technology from the lab of Nobel Prize winning Prof. Ada Yonath offers a tool in designing and developing new types of novel antibiotics. It is a high resolution crystal structure of the large ribosomal (50S) subunit from Staphylococcus aureus. The structure is based on a pathogenic strain giving new insight and capacity to target specifically the bacterium (Eyal Z, et al. (2015) Proc Natl Acad Sci and Eyal Z, et al. (2016) Sci. Rep.).

Applications


·         Designing and developing new types of antibiotics.

·         Computational screening of chemical libraries, reducing the number of physical compounds to screen.

·         Improving overall understanding of the ribosome in S. aureus.

·         New potential antibiotics binding sited which are species specific.


Advantages


·         High Resolution – the structure gives high detail and possible target positions for antibiotics.

·         Crystal Structures soaked with antibiotics – certain antibiotics have been soaked with the structure giving insight in how they interact with the ribosome, improving rational design of new antibiotics.

·         Structure based on pathogenic bacterium – improving targeting of antibiotics, as current bacterial ribosomal structures are based on non-pathogenic species.


Technology's Essence


The invention is a high resolution crystal structure of the large ribosomal subunit from the pathogenic S. aureus. The crystal structures importance is that it originates from a pathogenic species allowing for a high-degree of specificity in targeting the S. aureus ribosome. Rather than the currently available ribosomal structures based on non-pathogenic bacteria, where small differences between species may limit the effectiveness in a designed antibiotic. The importance of the technology is that MRSA (methicillin-resistant S. aureus), is becoming more common place in hospitals, care homes, and even in the agricultural sector. Thus there is a clear need for new types of antibiotics that can help to counteract the ever growing problem of bacterial antibiotic resistance.  

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  • Prof. Ada Yonath
1549
A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one...

A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.

Applications


  • Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)

Advantages


  • Effective blockade of the tumorigenic action of ErbB-specific ligands
  • The combination protocol may enhance the sensitivity to chemotherapy

Technology's Essence


In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.

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  • Prof. Yosef Yarden
1736
Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production. Improvement in the...

Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production.

Improvement in the metabolic pathway related to carbon fixation would have great value in increasing crop yields, synthesizing high value compounds in algae, and developing means in removing CO2 from the atmosphere to combat climate change.

The present technology is an engineered E. coli with a carbon fixation pathway. The unique innovation can be used to efficiently screen the activity of RuBisCO, the most abundant carbon fixing enzyme on earth, which is further applicable to improving biomass production in different photosynthetic organisms such as plants and algae.

Applications


·      Powerful platform for screening and improving various enzymes in the carbon fixation process.

·      Unique metabolic pathway for use in Synthetic Biology applications.

·      Possible Carbon Credits for developing improved means of carbon fixation.


Advantages


·      E. coli is fast growing and easily manipulated by various genetic tools.

·      Novel source of biomass production.

·      Potentially low cost R&D system.


Technology's Essence


The technology functions by the recombinant insertion of two enzymes from the Calvin-Benson-Bassham (CBB) into E. coli, kinase prk and the carboxylating enzyme RuBisCO. With further modifications, the engineered E. coli’s metabolism was divided into two subsections. First a carbon fixing metabolism that can incorporate inorganic CO2 into sugar production, the second subsection consumes organic pyruvate to produce energy to drive the aforementioned carbon fixing cycle. Subsequently the technology is overall carbon neutral, but is an inexpensive and fast platform for screening improvements in the CBB carbon fixation pathway.

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  • Prof. Ron Milo
1750
Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases...

Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.
Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases, with an exceptionally high potency. Although not as lethal as nerve agents, organophosphate insecticides can be harmful in large or prolonged doses. The standard therapy has limited efficacy, carry risks of serious adverse effects and have relatively short shelf life in field conditions.
Bioscavengers represent a preferred to rapidly detoxify organophosphates in the blood, before they had the chance to reach its physiological targets and cause damage, but usually require the use of very high doses.
The present invention provides genetically modified phosphotriesterase (PTE) variants, which serve as catalytic bioscavengers for V-type nerve agents, with exceptional detoxification activity at low doses, and improved stability.

Applications


  • Prophylactic or post exposure treatment for nerve gases attack, in particular V-type agents
  • Treatment for pesticides poisoning

Advantages


  • High catalytic activity – allow high efficacy at low doses
  • Reduced effective doses allows to reduce adverse effects
  • High stability increasing shelf life
  • Compatible with both prophylaxis and post exposure
  • Compatible for both surface decontamination and administration to patients

Technology's Essence


Researchers at Prof. Tawfik lab use directed evolution to drive protein mutagenesis towards desired traits. Appling this approach, using the actual threat agents, the present inventors generated recombinant phosphotriesterase (PTE) variants with improved catalytic efficiencies towards V-type nerve agent hydrolysis. Serving as catalytic bioscavengers, these recombinant PTE variants hydrolyze organophosphates without being consumed and thus can be applied at low doses (catalytic efficiency (kcat/KM) greater than 3.106 M-1min-1).
Importantly, PTE is efficient both as a prophylactic agent that may be given several hours prior to exposure as a preventive measure, and as post exposure antidote, even days after in a single or multiple-doses.
It is compatible with both decontamination of surfaces and detoxification administrated to a patient by standard routes such as orally or injectables.
Finally, some PTE variants show superior stability properties, retaining at least 50% of their catalytic activity at 50?C, indicating extended shelf life. This may be especially critical in field conditions, where the risk for nerve agent exposure is high.

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  • Prof. Dan S. Tawfik
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
1782
L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.Betalains are robust, flavorless, natural water soluble dyes,...

L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.
Betalains are robust, flavorless, natural water soluble dyes, in the color ranges of both red-violet and yellow-orange. Currently there is no natural quality source for water soluble natural yellow dyes, with present natural yellow dyes being water insoluble.
The present technology offers an alternative method that is simple, does not produce side-products, and is non-toxic with Tyrosine being the only feedstock. The technology produces L-DOPA and natural water soluble yellow and red Betalain dyes, both within yeast and in different plant species.

Applications


  • Production of L-DOPA for use in pharmaceuticals or dietary supplements.
  • Synthesis of water soluble yellow and red natural dyes for use as colorants, antioxidants, and food supplements.
  • Altering coloration of ornamental plants by inserting the metabolic pathway.

Advantages


  • One-step reaction for L-DOPA synthesis from Tyrosine.
  • Non-toxic and non-hazardous synthesis.
  • Ecologically friendly - no waste management issues.
  • Multiple colors can be produced with yellow, red, or orange if pathways combined.
  • Flavorless - avoid influencing the taste of different products.
  • Flexibility in biosynthetic production - multiple possible host systems.
  • Specificity - no side products produced
  • Mild Conditions - enzyme(s) requires ambient temperatures.

Technology's Essence


The present technology takes advantage of the Betalain biosynthetic pathway to selectively produce L-DOPA and natural Betalain dyes. A newly discovered, specific, cytochrome P450-CYP76AD6 begins the pathway, with the capacity to convert Tyrosine to L-DOPA. Then L-DOPA is converted to Betalamic acid via DOPA 4, 5-dioxygenase.
With the Betalamic acid intermediate, the biosynthetic pathway diverges to make either Betaxanthins (yellow dyes) or Betacyanins (red dyes). In the production of yellow dyes an amine (e.g. amino acid) spontaneously reacts with Betalamic acid. In the case of red dyes, cycloDOPA (generated by the enzyme CYP76AD1 modifying Tyrosine and L-DOPA) and a Betalain-related glucosyltransferase react with Betalamic acid. Furthermore the two pathways can be done in parallel to produce an orange color.

 

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  • Prof. Asaph Aharoni
1679
A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combinationBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect...

A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combination
Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect women at a younger age. Unfortunately TNBC cannot be treated with the common receptor targeted therapies since it does not express these targets, the estrogen, progesterone and Her2/neu receptors. Therefor systemic treatment options are currently limited to cytotoxic chemotherapy. The lack of effective targeted therapies, resistance to chemotherapy, and early metastatic spread have contributed to the poor prognoses and outcomes associated with TNBC.
The current technology offers a novel therapeutic strategy for TNBC. The application of two novel, noncompetitive antibodies against EGFR, achieves a robust degradation EGFR resulting in tumor inhibition.

Applications


  • Novel and unique antibody targeted therapy for TNBC.
  • The novel anti EGFR antibodies can cooperate synergistically with the currently marketed EGFR antibodies.

Advantages


  • A promising therapeutic scenario to treat TNBC.
  • Enhanced EGFR degradation and improved anti-tumor activity, in contrast to clinically approved anti-EGFR mAbs, which display no cooperative effects.
  • Lysosomal EGFR degradation pathway induced by epitope-distinct antibody mixture may potentially lead to improved therapeutic outcome, and reduced resistance.

Technology's Essence


Prof. Yosef Yarden and his team demonstrated that a combination of novel antibodies that target distinct regions on the human EGF receptor resulted in its robust and synergistic down-regulation, leading to pronounced tumor growth inhibition. Furthermore, the combined mAbs induced lysosomal degradation of EGFR, while avoiding the recycling route. Such irreversible mode of EGFR degradation may potentially increase response rate or delay the onset of patient resistance.
Conversely, combining cetuximab and panitumumab, the mAbs routinely used to treat colorectal cancer patients, did not improve receptor degradation because they are both attracted to the same epitope on EGFR.

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  • Prof. Yosef Yarden

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