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1527
New peptides for improving the recruitment of stem cells for transplantation. Blood cancers (leukemia, lymphoma and myeloma) are very common: they accounted for nearly 9.5 percent of deaths in the US from cancer in 2009. Stem cell transplantation, which aims to restore the function of the marrow, is an...

New peptides for improving the recruitment of stem cells for transplantation.

Blood cancers (leukemia, lymphoma and myeloma) are very common: they accounted for nearly 9.5 percent of deaths in the US from cancer in 2009. Stem cell transplantation, which aims to restore the function of the marrow, is an important therapy for these malignancies. Successful blood and marrow transplant requires the infusion of a sufficient number of hematopoietic stem and progenitor cells (HSPC), which is done by recruitment of HSPC from the marrow into the blood (mobilization). Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with chemotherapy. However, some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. Hence, improved methods to mobilize peripheral blood HSPC are warranted. The present invention is directed to novel short peptides of beta-defensins for improving the mobilization of HSPC.

Applications


  • Rapid and efficient mobilization of HSPC for clinical transplantation
  • Inhibition of malignant cell proliferation and metastasis

Advantages


·         Non-toxic, derived from a physiological molecule of innate host immunity

·         Cheap and simple synthesis

·         Rapid, robust and preferential mobilization of immature HSPC

·         Enhancement of mobilizing efficiency of presently used substances (e.g. G-CSF)

·         Dual use of the derivatives


Technology's Essence


Beta-defensins belong to a family of antimicrobial peptides, a major component of the innate immune system. In a mouse model, two different linear beta-defensin-derived peptides provided a strong and rapid HSPC mobilization, alone and in combination with G-CSF, a cytokine that is the major agent inducing robust mobilization of HSPC. In addition, a cyclic peptide derivative effectively inhibited HSPC mobilization and proliferation, as well as human malignant cell motility in mice. These findings make beta-defensin-derived peptides as promising small molecule candidates for improving current clinical HSPC mobilization protocols, and their cyclic derivatives as promising candidates for reducing cancer cell development and metastasis in patients.

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  • Prof. Tsvee Lapidot
1378
Researchers at the Weizmann Institute developed a novel method to design error-free DNA libraries from error-prone oligonucleotides. The system surpasses existing methods for de novo synthesis of DNA libraries in speed, precision, amenability to automation and ease of combining synthetic with natural...

Researchers at the Weizmann Institute developed a novel method to design error-free DNA libraries from error-prone oligonucleotides. The system surpasses existing methods for de novo synthesis of DNA libraries in speed, precision, amenability to automation and ease of combining synthetic with natural DNA fragments. 

All DNA construction protocols struggle with the cumbersome task of cloning and sequencing synthetic DNA fragments, seeking an error-free one. The problem is worsened for longer synthetic DNA which is more prone to errors. Time spent on error correction, clone selection and sequencing is a major bottleneck that prevents de novo DNA synthesis from becoming a routine procedure in labs. 

This innovative solution significantly decreases the need for labor-intensive time-consuming error correction methods, cloning and sequencing. Furthermore, efficient editing and reassembly of different genes is made possible due to a smart recursive reconstruction process.

 

Applications


  • Design and construction of synthetic biological molecules and organisms.
  • Construction of designer DNA libraries.

 


Advantages


  • Applicable in any lab with standard lab equipment. Faster and more precise than existing methods.
  • Amenable to automation, full synthesis in vitro with a modified smPCR protocol.
  • Very simple to combine synthetic and natural DNA fragments.
  • Does not require additional or external methods or reagents for error correction

 


Technology's Essence


Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed.

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  • Prof. Ehud Y. Shapiro
1655
Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and...

Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and promote a number of pathological conditions. Therefore the elimination of senescent cells is desired in order to prevent tumor- and inflammation- related pathologies and also to inhibit tissue ageing.
Today, our understanding of the mechanisms regulating the viability of senescent cells is limited. It has been suggested that senescent cells are resistant to apoptosis. Therefore, senescent cells elimination may be achieved by modifying the resistance to apoptosis of these cells.
Here the researches demonstrate the first feasible therapeutic approach that leads to eradication of senescent cells. Combination of direct induction of apoptosis in senescent cells with induction of cell death by pro-inflammatory repose induce by p21 knockdown will lead to reduction of viable senescent cells.

Applications


  • A therapeutic impact on inflammatory and fibrotic disease
  • Therapy for age-related disease such as type 2 diabetes, Alzheimer’s disease, Atherosclerosis, cataracts, Chronic obstructive pulmonary disease (COPD), and Osteoporosis

Advantages


  • Effective elimination of senescent cells- removal of senescent cells can prevent or delay tissue dysfunction and extend health span
  • Does not damage normal cells even at high concentrations

Technology's Essence


Researches demonstrated that the anti-apoptotic proteins Bcl-xL and Bcl-w level were elevated in senescence cells of both human and mouse origin. A subsequent study, in which Bcl-xL and Bcl-w were knocked down by siRNA, revealed that a combined knock down of Bcl-xL and Bcl-w had synergic effect, resulting in reduction of 50% in cell viability. Thus the increased level of anti-apoptotic proteins Bcl-xL and Bcl-w may account for the apoptotic resistance of senescent cells. p21 knockdown induced pro-inflammatory response and cell death in senescent cells.
Overall, the researchers show that combined inhibition of the anti-apoptotic proteins Bcl-xL and Bcl-w allows specific elimination of senescent cells and might be used to treat diseases where senescent cells are present. The researchers also found that the same effect might be achieved by reducing the expression of p21 in senescent cells. Integrating both approaches propose a more effective therapy.

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  • Ph.D. Valery Krizhanovsky
1668
Despite progress in early detection and treatment, breast cancer remains a leading cause of cancer-related death in women. For example, in 2012 alone, 41,150 women in the United States died from breast cancer. Targeted therapies, which are based on oncogenic genetic abnormalities, are commonly used to...

Despite progress in early detection and treatment, breast cancer remains a leading cause of cancer-related death in women. For example, in 2012 alone, 41,150 women in the United States died from breast cancer.

Targeted therapies, which are based on oncogenic genetic abnormalities, are commonly used to treat subgroups of breast cancer patients. Although these treatments show promising results, they are limited to only a subgroup of patients (for example, amplification of HER2 occurs in about 15% of breast cancers) and there is an unmet need for the identification of druggable targets with a major oncogenic role in breast cancer development.

The present invention relates to the identification of SYNJ2 as a novel target for breast cancer treatment. SYNJ2 expression is enhanced in a sub-population of breast cancer patients and its catalytic activity was shown to promoted cell migration and invasion. Furthermore, screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration, suggesting that SYNJ2 is a potential target for cancer treatment.

Applications


 


Advantages


  • Novel identification of SYNJ2 as a genetically aberrant and potentially druggable driver of tumor progression.
  • Specificity – the discovered SYNJ2 inhibitors do not inhibit SYNJ1 which plays additional roles in the nervous system.
  • Potential therapeutic effect – Inhibition of SYNJ2 in several cancer models blocks tumor progression and invasion.


Technology's Essence


SYNJ2 abundance is increased in breast tumors and it is correlated with poor prognosis and aggressive subtypes of breast cancer. Furthermore, growth factors involved in breast cancer metastasis can increase SYNJ2 expression in association with increased cell invasion.

SYNJ2 is localized to cellular protrusions involved in migration and matrix invasion and its phosphatase activity enhances tumor growth and metastasis in mice. Unlike wild-type SYNJ2, reexpression of a catalytic inactive mutant failed to restore invasiveness of cancer cells, indicating that the catalytic activity of SYNJ2 is essential for motility.

Using a high-throughput screening platform for the measurement of SYNJ2 activity, four specific SYNJ2 inhibitors were discovered. All of the four inhibitors were selective to SYNJ2 and didn’t have an effect on its brain-enriched kin, SYNJ1. In addition, all four compounds attenuated cellular invasion, suggesting that specific SYNJ2 inhibitors can be developed as potential drugs for cancer therapy.

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  • Prof. Yosef Yarden
  • Prof. Yosef Yarden
1498
MicroRNAs as potential biomarkers for ALS.Amyotrophic Lateral Sclerosis (ALS) is a devastating disease that progressively destroys motor neurons in the brain and the spinal cord, eventually causing paralysis and death. Currently, there are approximately 25,000 patients with ALS in the USA, with a...

MicroRNAs as potential biomarkers for ALS.
Amyotrophic Lateral Sclerosis (ALS) is a devastating disease that progressively destroys motor neurons in the brain and the spinal cord, eventually causing paralysis and death. Currently, there are approximately 25,000 patients with ALS in the USA, with a median age of onset of 55 years. Approximately 5–10% of patients with ALS have a family history, and these patients most frequently inherit the disease in an autosomal dominant manner. Family-based linkage studies have led to the identification of several genes for familial ALS. However these findings only explain a small fraction of all ALS cases. The majority of ALS cases have no obvious family history and are referred to as sporadic ALS. At present, there is no effective therapy for the disease and patients usually die within 2-5 years after the onset of symptoms. Thus, there is an urgent need for biomarkers that could substantially aid early diagnosis of ALS and will help in designing decisive clinical trials of new drugs. The present technology provides specific microRNAs that can serve as potential biomarkers for ALS.

Applications


  • Unique patterns of microRNA expression profile in the cerebrospinal fluid of ALS patients could be useful as molecular biomarkers for disease diagnosis and eventually prediction of therapeutic responses.
  • The suggested ALS biomarkers may be employed in drug development studies.

 


Advantages


  •  MicroRNAs can be precisely quantified using qRT-PCR that provides exceptionally high sensitivity and specificity of detection.
  • The small size of microRNAs offers a unique advantage since they are more stable and less prone to enzymatic degradation, and are therefore amenable to an accurate assessment of their expression levels.

Technology's Essence


MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression in a posttranscriptional fashion and contribute to a wide variety of biological processes. miRNAs play important roles in the development of the central nervous system and their involvement in neurodegenerative diseases such as Parkinson's disease and Alzheimer’s disease has been recently established. The outlined technology describes specific miRNAs that are enriched in motor neurons and are significantly downregulated in mouse models of hereditary motor neuron disease (SOD1G93A and SMN1). These miRNAs may serve as putative biomarkers for motor neuron diseases such as ALS by measurement of their expression levels in cerebrospinal fluid samples collected from affected individuals.

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  • Dr. Eran Hornstein
1698
GD is an inherited metabolic disorder, affecting about 1 in 20,000 births. GD is divided into three clinical subtypes: type 1 is the most common and is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. Types 2 and 3, also called neuronopathic GD (...

GD is an inherited metabolic disorder, affecting about 1 in 20,000 births. GD is divided into three clinical subtypes: type 1 is the most common and is characterized by bruising, fatigue, anemia, low blood platelets, and enlargement of the liver and spleen. Types 2 and 3, also called neuronopathic GD (nGD), affect 4% of GD patients and additionally include neurological symptoms. Type 1 patients can have a normal life expectancy if treated whereas type 2/3 patients do not survive to reach adulthood. Moreover, GD carriers, approximately 1% of the population, are in a major risk of developing Parkinson’s disease. Current therapies suffer from severe drawbacks in the treatment of type 1 GD and no therapy exists that effectively treat nGD. The present technology offers a novel therapeutic target for the treatment of Gaucher's disease (GD) which addresses also the neurological symptoms.

Applications


  • Alternative treatment for type 1 GD
  • First line therapy for nGD

Advantages


  • A novel therapy for nGD which has no treatment for the present.
  • A novel therapeutic approach for GD type 1, via a previously unknown molecular mechanism.
  • Allows the development of an orally administered treatment, far more convenient for the patients than the existing treatments.
  • Reduced costs compared to the existing therapies of ERP or BMT

Technology's Essence


The proposed technology is based on the discovery that RIP3 is a key player in the manifestation of GD and that inhibiting RIP3 activity is effectively ameliorating the symptoms of GD not only in the less severe type 1 but also in the neuropathic form of the disease, types 2 and 3. nGD is associated with a massive neuronal loss and elevated RIP3 levels. Inhibition of RIP3 in a mouse model of nGD resulted in a dramatic attenuation of disease signs: drastic extension of life span, no weight loss, improvements in motor coordination, reduced neuroinflammation and improved liver and spleen injuries.

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  • Prof. Anthony H. Futerman

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