The Life Sciences Project Bulletin

   

 

New Projects in

 

Gene and Cell Therapy

 

from Israel

 

No.19 – June 2004

                                            www.optin.nl

 

Projects

 

1.      Oncolytic Herpesvirus Amplicon Vectors for Cancer Gene Therapy

 

2.      A New Method for Introducing Large Molecules and Genes Into Cells Based on Transient Chemical Disruption of the Cell Membrane

 

3.      Enrichment Of Repopulating Stem Cells For Clinical Protocols

 

4.      Using bioluminescence to monitor gene expression in live experimental animals:  the first step in developing a human gene imaging machine

 

5.      New protocols and procedures that focus on cell therapy

 

6.      Mesenchymal Stromal Cell (MSC) Use for Cell Therapy and Tissue Engineering

 

7.      Gene Delivery by Sv40 Pseudovirions and Their in Vitro Packaging

 

8.      Mucosal immunization for viral infections

 

9.      Development of closed-chest delivery systems for myocardial gene therapy

 

10.   Beta-cell replacement in type 1 diabetes: the promise of stem cells

 

11.   Herpesvirus Amplicon Vectors for Vaccination

 

12.   Gene delivery system involving a new vector for gene therapy

 

13.   Novel devices for cell-therapy

 

14.   Multi-fold expansion of hemopoietic stem cells with minimaldifferentiation

 

15.   New gene transfection agent for gene therapy

 

16.   Multi-Gene Vascular Systems

 

17.   Development of oncolytic viruses intended for cancer therapy

 

18.   Unique vectors for gene therapy constructed in the test tube from purified components of a pseudo-virus

 

19.   Novel therapy for atrial fibrillation based on Gene Therapy

 

20.   Cell therapies and other treatment strategies for neurological, ophthalmologic and immune-related disorders

 

21.   Expanding human umbilical cord blood banks

 

22.   Development of gene delivery tools and anti atherosclerotic agents to better address cancer and cardiovascular diseases

 

23.   Novel tools for research in molecular biology and medicine

 

24.   Laboratory kit for measuring genetic expression

 

 

 

In the News

 

1.    What is Gene Therapy?

 

2.    Intel Israel heralds chip breakthrough

 

3.    U.S. and Israeli Nanotech researchers set sights on clean water

 

 

Advertorials

 

1.      Sigma-Aldrich Corp. conducts research and development

2.      Health-Invest: The New Dutch magazine for Life Sciences

 

 

Announcements

 

1.      EOI's for the Sixth Framework

 

 

Coming up in the next bulletins:

New projects inPlant Biotechnology and Tissue Culture”

 

 

Publish your projects in the Life Sciences Project Bulletin

 

Projects from the previous Bulletins

 

For more information contact Optin’s Director Drs. Jennifer Peersmann or call +31-(0)70-3643260

 

For background and contact information per project contact: Optin’s Life Sciences Manager Drs. Eli Guetta

 

 

 

 

Events

 

International Congress on Medical and Care Compunetics

 

2-4  June 2004

 

NCC (Netherlands Congress Centre), The Hague, The Netherlands

 

Genomics Momentum

 

30 August - 1 September 2004

 

De Doelen Congress Centre, Rotterdam, The Netherlands

 

AQUATECH Trade Fair

 

28 September – 1 October 2004, includes Nanotechnology and Water Conference on Monday the 27th of September

 

Europa Complex (Halls 1 to 7), RAI Exhibition and Conference Centre, Amsterdam, The Netherlands

 

 

 

 

Sponsors

Health Invest

 

The Embassy of The Netherlands

 

The Embassy of Israel

Matimop

 

MXCard: Profetional Marketing and Customer

Relations Tools

 

DSM Venturing

 

IBM Life Sciences

 

Tel Aviv University

 

Teva Pharmaceutical Industries Ltd

 

Eden’s Creations/ Hoekert

 

Holland Biotechnology

 

WFIA / Israel Office Delft

 

Rad-Biomed Incubator

 

CIDI

 

 

Contributors

Ramot / Tel Aviv University

IRC / Senter

Yissum / The Hebrew University

BMTI / TU-Twente

Yeda / Weizmann Institute

Rad-Biomed Incubator

Hadasit

Technion

Bar Ilan University

Ben-Gurion University

Matimop

 

 

Projects

Oncolytic Herpesvirus Amplicon Vectors for Cancer Gene Therapy

We describe the derivation of composite oncolytic vectors for potential use in gene therapy of  (i) solid tumors such as lung carcinoma and brain tumors (ii) T cell lymphomas.  The vectors are derived from Herpes simplex virus–1 (HSV-1) which targets cells from solid tissues, including skin and neuronal cells; the Human herpesviruses 6 and 7 (HHV-6 and HHV-7), which target human lymphocytes. When compared to other available vectors the amplicon vectors are advantageous due to: (i) large transgene capacity; (ii) sequence reiterations leading to efficient gene expression;  (iii) the vectors can be inhibited by drugs, raising vector safety.  The new genes include toxic genes (such as p53), which cause death of tumor cells and genes that increase the host’s natural immune response against the tumor. Helper viruses used for the production of the amplicon vectors contain alterations (mutations) disabling their replication and spread, and making the vector safe for use. The combination of vector and helper virus produce efficient tumor cell death and sensitivity to x irradiation, in addition to raising immunological anti-tumor response. Preliminary studies have shown prolonged survival of vector treated mice carrying xenografts of human tumor tissues.

 

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A New Method for Introducing Large Molecules and Genes Into Cells Based on Transient Chemical Disruption of the Cell Membrane

Introduction of foreign DNA and antisense oligodeoxyribonucleotides (ODN) into cells is a critical process in molecular biology research, in biotechnology, and in gene based therapies. Six different techniques are now available for this purpose. Each has its advantages and drawbacks. This new invented technique has the potential of being both dependable and less harmful to the cells and thus is likely to become the best method for introducing large molecules into cells. The procedure offers a new versatile and dependable method for introducing large molecules into cells. It has the potential of being the preferred technique in various fields such as gene therapy and biotechnology. The process is based on earlier unpublished observation on transient removal of the membrane barrier by chemical methods. The procedure is now being tested as a gene transfecting device in several types of cells. Future  plans include development of a special device that allows a very accurate and short (i.e. up to milliseconds) disruption of the membrane barrier for refinement of the method.

 

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Enrichment Of Repopulating Stem Cells For Clinical Protocols

During development and in clinical bone marrow transplantation, stem cells migrate to the bone marrow. Stem cells continuously produce all mature blood cells and are defined in functional repopulation assays based on their ability to home to the bone marrow microenvironment and to durably repopulate transplanted recipients with both myeloid and lymphoid cell. Others and we  developed functional in-vivo assays for human stem cells by transplanting them into immune deficient NOD/SCID mice. We identified primitive human SCID repopulating cells (SRC), which provide a means to measure the multilineage engraftment properties of transplanted human stem cells as a pre clinical model. In addition, this model was also used to identify malignant SCID Leukemia Initiating Cells (SLIC), based on their ability to initiate the disease in transplanted mice. Recently we have extended the use of these models to identify and characterize the role of chemokines, cytokines, adhesion molecules and stromal cells in stem cell migration and repopulation. New Invention Stem cell homing and engraftment require several adhesion interactions, which are not fully understood. We discovered that the chemokine stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 are crucial for murine bone marrow engraftment by human SCID -repopulating stem cells. Treatment of human cells with antibodies to CXCR4 prevented engraftment. In addition, we discovered that SRC engraftment of NOD/SCID mice is dependent on activation of the major integrins LFA-1, VLA-4, and VLA-5 by SDF-1. Treatment of human cells with antibodies to either of these integrins also prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of primitive CD34+ /CD38-/low cells correlated with in vivo engraftment and stem cell function. The cytokines stem cell factor (SCF) and IL-6 induced CXCR4 expression on immature cells, which potentiated migration to SDF-1 and engraftment in primary and secondary transplanted mice. Primitive CD34 -/CD 38-/low cells also express CXCR4, migrate to SDF-1 and engraft NOD/SCID mice. Our results characterize human stem cells as CXCR4+ CD38-/low cells, which functionally express LFA-1, VLA-4 and VLA-5. Thus, upregulation of CXCR4 may be useful for improving engraftment of repopulating stem cells in clinical transplantation. Applications: To establish human stem cell enrichment kits which are based on expression of CXCR4, integrins and migration to SDF-1, but not on expression of CD34. To improve clinical stem cell transplantation by increasing the levels of repopulating CXCR4+ stem cells in vitro before transplantation by cytokine stimulation and by improving purging of malignant cells based on their lack or reduced migration levels to SDF-1.

Project Number: ls1005, Department: Immunology,  Weizmann Institute, Israel.

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Using bioluminescence to monitor gene expression in live experimental animals:  the first step in developing a human gene imaging machine

We are developing an efficient, non-invasive system for monitoring the targeting, expression amplitude, and expression duration of transgenes in living animals.  Our system is based on the use of the firefly luc gene whose gene product, luciferase, converts luciferin into a bioluminescent substance.  The photons emitted by this bioluminescent substance can be detected by a Charged Coupled Device (CCD) Camera equipped with a microchannel plate intensifier system.  This method has a broad range of applications for many tissues and vectors.  Coupling the expression of a chosen gene to that of luc will facilitate the on-going monitoring of transgene expression and that in turn could expedite the generation of individualized therapies and vaccination protocols.  Furthermore, the system can be used to monitor the growth rate of tumor cells in a given organ.  Thus, this in vivo, quatitative luc-based imaging system opens new routes for many applications in gene and cell therapy, vaccination, and tumor development models, as well as the study of in vivo gene expression.  The method is expeditious and prevents the needless sacrifice of experimental animals at each experimental time point.  In addition, we plan to use the results of our research to develop a machine for human gene imaging, that will join the ranks of technologies like CAT scans and MRI. The development of new programs for gene therapy requires the assessment of the in vivo delivery and expression of transgenes.  The methods currently in use are all complex, and it is not yet possible to compare the results from various methods.  Furthermore, most of these are expensive because they require the sacrifice of experimental animals at each time point.  In the presence of oxygen and ATP, luciferase, the product of the firefly luc gene, converts luciferin to an active bioluminescent substance.  Since it has a linear dose response over a wide range of concentrations, luc has become a commonly used reporter gene for both in vitro and in vivo studies.  This emission can be detected using a CCD Camera equipped with a microchannel plate intensifier system.  Such a camera can detect low amounts of photons emitted by internal mammalian tissue both in vitro and in vivo.  This system is suitable for quantitatively monitoring the organ targeting and real-time kinetics of both viral vectors and of ex-vivo manipulated cells in a single mouse over a long period of time. We used one in vitro and four in vivo systems:  a) HepG2/luc cells grown in culture; b) HepG2/luc cells grown in vivo in mice after subcutaneous or c) intrasplenic administration; d) mice injected with recombinant adenoviruses expressing luc under the control of an SV40 promoter; and e) mice injected with recombinant adenoviruses expressing luc under the control of the HIV-1LTR promoter.  At each time that we wished to measure the placement or the expression amplitude of the luc gene, we administered a measured dose of luciferin.  In each case, using the CCD camera equipped with a microchannel plate intensifier system, we were able to detect both the placement and the level of the luciferase enzyme activity.  We found SV40 dependent luc to be restricted to the liver; we confirmed this by surgically partially separating the liver and measuring the photon emission from that external position.  The expression over time of this vector suggests that it could be used to assess the activity of various liver-specific regulatory elements that could then be used to control the genes coding for various therapeutic proteins.  This method should be valuable for other tissues and vectors as well.  HIV-LTR dependent luc was detected in the region of the testis but was not detected in the liver. Key words:  transgenes, gene therapy, bioluminescence, in vivo gene expression, cell therapy, tumor cells.

 

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New protocols and procedures that focus on cell therapy

New immunotherapy protocols and procedures that focus on adoptive allogeneic cell therapy, cytokines, targeted chemotherapy and tumor cell vaccination, are already being clinically applied for resistant acute and chronic leukemias, Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, myelodysplastic syndromes and metastatic solid tumors, as well as adoptive allogeneic cell mediated immunotherapy for hematological malignancies, utilizing naïve, cytokine- and tumor-specific or rather tumor-reactive lymphocytes, and cytokine research. The work being carried out on new cancer cell vaccines constitutes an attempt to up-regulate and stimulate the patient’s immune system to fight residual tumor cells using specific and non-specific agents and tumor-specific antigens as well as allogeneic tumor cell vaccines containing common antigenic epitopes.  In parallel, new approaches are being developed to down-regulate and control the immune system towards induction of specific unresponsiveness, with the aim of reducing self-reactivity in life-threatening autoimmune diseases on the one hand, and inducing permanent and specific transplantation tolerance to bone marrow, tissue and organ allografts on the other. Much effort is being devoted to the control of acute and chronic graft-versus-host disease (GVHD). Work is also proceeding on gene therapy with the aim of manipulating abnormal stem cells and T cells serving as anti-cancer effector cells for the treatment of certain immune deficiencies and, hopefully, other genetic disorders in the future. Recent research projects involve stem cell plasticity, focusing on the regeneration of bone and cartilage for the correction of the osteo-hematogenic complex, and bone and joint diseases.  A recently established chemistry laboratory is engaged in the design of new molecules for better control of the immune system and for targeted cancer therapy, with emphasis on small molecules that can be orally administered.

 

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Mesenchymal Stromal Cell (MSC) Use for Cell Therapy and Tissue Engineering

Mesenchymal stromal cells derived from the bone marrow (MSC) maintain the bone remodeling and differentiation of hemopoietic cells. The stroma function is based on cells that may be differentiated into various subtypes such as fibroblasts, osteogenic and muscle cells that are derived from a common stem cell. MSC have a broad use in cell therapy and tissue engineering. At Tel Aviv University stromal cell research is being conducted in the Faculty of Medicine by a group headed by Dr. D. Benayahu with the aim of exploring the question of MSC identity. Before MSC can be used for cell therapy, we first have to discover how to recognize the specific marrow stromal cells. The goal in the research is to develop a molecular and biochemical approach that will enable the isolation and identification of progenitor cells down through their lineages. A series of known and novel markers cloned in Dr. Benayahu laboratory allows the identification and selection of stromal subpopulations. In this research we applied an ex vivo system to expand MSC and to compare their in vitro and in vivo properties. The novel markers cloned in the laboratory are useful tools for clarifying the mechanisms that control the cell differentiation as a matter of transcriptional regulation. The genes identified are key regulators in the control of stromal stem cell differentiation. These markers provide an attractive clue for studying how to modulate MSC in vitro and in vivo and to control their maturation through specific lineage. The study deepens knowledge on genes and protein structure and function, enabling us to follow MSC differentiation. Alterations in these genes will serve as genetic tools for an understanding of bone, skeletal and cardiac muscle disorders. The project provides important tools for both cell selection towards their use in cell therapy and the development of treatment strategies for a wide spectrum of pathological states.

 

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Gene Delivery by Sv40 Pseudovirions and Their in Vitro Packaging

We have developed a vector based on a small DNA virus named SV40, which in nature causes a mild viral illness in primates. In the vector, over 95% of the viral genetic material is replaced with curative, normal human genes, resulting in a particle called a pseudovirus. The SV40 vector is potentially suitable for gene therapy of a wide spectrum of diseases. This is due to its high efficiency in gene transfer into a wide variety of human cells, including cells of the bone marrow which are the critical target of treatment for many diseases. Our unique SV40 pseudoviral vector has many advantages over other currently available vectors. It has a very wide host range and high efficiency in gene transfer. It is most efficient with hematopoietic cells, the target of choice for the treatment of many diseases. Moreover, it can infect non dividing cells, such as the human bone marrow stem cell. SV40 pseudovirions prepared by the recently developed method of in vitro packaging combine the efficiency of gene delivery of a viral vector with the safety and purity of non viral vectors.  An ideal way to prepare pseudovirions for therapeutic purposes for human use is by in vitro packaging. This method provides maximal safety, since all steps of the preparation can be well controlled. Furthermore, this method is suitable for biotechnological production.  This technology serves as the basis for the new early stage biotechnology company, Gene Vector Technologies Ltd.

 

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Mucosal immunization for viral infections

Infectious diseases are a worldwide cause of morbidity and mortality.  Such diseases particularly affect individuals with weaker immune systems, such as children, and are probably the primary worldwide killer of children (The World Health Report 1997, WHO). Travel and other contact between populations have caused the world to become an increasingly mixed environment in terms of the spread of micro-organisms, such as bacteria and viruses, thereby demanding a higher degree of protection for communities from such infectious agents. In particular, no mass vaccination program exists for Hepatitis A virus (HAV). HAV vaccine is currently generated in tissue cultures, which produce a low viral titer, and is therefore expensive.  The expense and difficulty of production are such that the HAV vaccine can currently only be purchased for small-scale programs. New modes for cheap and effective mass vaccination are needed. Providing a vaccine through a simple method could significantly increase the number of protected populations. Recently, a number of investigators have suggested that vaccination against bacterial agents, such as salmonella, or viral agents, such as HIV, may possibly be enhanced through the rectal administration of attenuated or killed bacteria. Rectal, nasal or oral administrations of vaccines have elicited a humoral and in some cases cellular immune response, although such a response has been variable, indicating that vaccines against certain infectious agents may not be successfully administered through one or more of these routes of administration. For some of these vaccines, however, the humoral response generated neutralizing antibodies against the pathogen as proven in the case of the polio oral vaccine developed by Alfred Sabin. Unfortunately, no such method for administering the HAV vaccine has been successful through a route of administration other than injection.  Therefore, the HAV vaccine is currently difficult to administer, such that any mass vaccination program would be expensive and complicated to perform. There is thus a need for, and it would be useful to have, a method for administering the HAV vaccine through a route other than direct systemic injection. The present invention relates to a method of immunizing a subject against Hepatitis A virus (HAV), and in particular, to such a method in which a vaccine against HAV is administered through the rectal mucosa of the subject. We developed a method for administering the HAV vaccine to a subject by absorption through a mucosal tissue, particularly through the mucosa of the rectum.  The method of the present invention enables the HAV vaccine to be administered to the subject rectally as a suppository, and to successfully immunize the subject against HAV.  Thus, the present invention overcomes problems such as systemic administration by injection for example, which require needles, and which are difficult and expensive to perform.

 

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Development of closed-chest delivery systems for myocardial gene therapy

Development of closed-chest delivery systems for myocardial gene therapy. We developed a delivery system, based on a balloon catheter, acetylcholine and echocardiographic contrast, to deliver reporter gene-encoding adenoviral vectors in a rat model. This study demonstrated that the system is significantly more efficient than each one of its components alone. We are currently testing a modification of this system in a large animal model (sheep) using adeno-associated virus as a vector.

 

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Beta-cell replacement in type 1 diabetes: the promise of stem cells

Type 1 diabetes mellitus is characterized by a progressive loss of pancreatic b cells, leading to insufficient insulin production. Beta-cell replacement is considered the optimal treatment for type 1 diabetes; however, the availability of human organs for transplantation is limited. An effective cell replacement strategy depends on the development of an abundant supply of b cells and their protection from immune destruction. Stem/progenitor cells, which can be expanded in tissue culture and induced to differentiate into multiple cell types, represent an attractive source of cells for generation of cells with beta-cell properties: insulin biosynthesis, storage, and regulated secretion in response to physiological signals. Embryonic stem cells have been shown to spontaneously differentiate into insulin-producing cells at a low frequency, and this capacity could be further enhanced by soluble agents. Progenitor cells from fetal and adult tissues, such as liver, have also been shown to be capable of differentiation towards the beta-cell phenotype in vivo, or following expression of dominant transcription factors in vitro. We explored whether human fetal liver progenitor cells  (FH) could be induced to differentiate into insulin-producing cells following expression of the pancreatic duodenal homeobox 1 (Pdx1) gene. The replication capacity of FH cells was extended by introduction of the gene for the catalytic subunit of human telomerase. The Pdx1 gene was introduced into these cells using a lentivirus vector carrying a neomycin resistance selection gene. Cells expressing Pdx1 activated multiple b-cell genes, produced and stored considerable amounts of insulin, and released insulin in response to physiological concentrations of glucose. The cells restored and maintained euglycemia for prolonged periods of time in hyperglycemic immunodeficient mice. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. We conclude that Pdx1 expression induces differentiation of human fetal liver cells into cells with b-cell properties. This approach offers novel ways of generating cells for transplantation into patients with type 1 diabetes.

 

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Herpesvirus Amplicon Vectors for Vaccination

When viruses infect their host, they trigger an immune response, which recognizes the proteins making up the viral particle.  A complex series of events follows, with eventual destruction of the virus. If the virus infects again, an immediate response, produced by “memory cells” abolishes the virus before it can spread, causing disease. In anti-viral vaccination, an engineered vaccine composed of weakened virus, or containing viral protein(s), is placed in the host, mounting a memory immune response capable of virus destruction upon potential infection.  We have derived viral vectors, which infect lymphocytes for gene therapy and vaccination by introducing selected proteins into the host without harming it.  The vectors, termed “amplicon-6,” contain multiple repeats of DNA replication and packaging signals of Human Herpesvirus–6, as well as repeats of the selected foreign genes, including selected proteins, as well as chosen chemokines designed to increase immune response. Exemplary transgenes include: (i) the major cell surface protein of herpes simplex virus (HSV) to be employed toward vaccination against facial and genital herpes infections; (ii) the envelope protein of HIV, toward development of an ADIS vaccine; (iii) the MUC1 protein, which is heavily expressed in human breast carcinoma. The amplicon-6 vector containing the MAC1 protein is employed to raise specific anti-tumor immune response.  All these exemplary proteins are expressed most efficiently in the target cells destined to raise immune response. Further studies will involve following the vaccination in animal model systems.

 

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Gene delivery system involving a new vector for gene therapy

The technology is based on the characteristics of viruses as natural carriers of genetic material to organism cells. By making

particular alterations to the virus it may be made to perform specific desired functions in carrying genetic material to cells, e.g., to restore damaged cells. Virus capsules are used as DNA packaging. Today various technologies utilize viruses as carriers to tissue cells in the body. The proposed technology utilizes the viral vector SV40 and its preparation in a test tube from controlled composites, yielding a pseudo-virus for use as a vector for gene therapy. The procedure that is carried out in the test tube will be more efficient and better controlled than if it was carried out in a cell culture. At this point there are no known competitors. The product will be:  1. A platform of original material for development of drugs on a genetic basis, to pharmaceutical companies that deal with the development of gene therapy. 2. A ready vector, for specific therapeutic purposes for hemopoietic cells. 3. For laboratory research. The potential market is infinite. Some of the diseases suitable for treatment by genetic therapy are: hereditary diseases, various cancers, viral diseases and diseases of the blood. Advantages: * Enables controlled protein production and thus an accurate desired affect on cells. * Revolutionary in its field - brings gene therapy research to a more advanced level.

 

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Novel devices for cell-therapy

Epigenesis is a biotechnology company, which develops cell-therapy based products. Epigenesis pipeline include a

bio-artificial liver device (aLIVE), a bio-artificial kidney device (Renal+) and a cell-therapy approach to induce angiogenesis (angiopump). ** aLIVE - an extra-corporeal bio-artificial liver device. aLIVE is being developed for the treatment of acute liver failure (FHF), chronic liver failure (Cirrhosis and Hepatitis) and replacement of liver transplant. aLIVE is the only device in

development that performs synthetic liver functions such as transcription of mRNAs coding for albumin and for clotting factors.

** angiopumps - induction of new blood vessels developed for treatment of Coronary Artery Disease (CAD), Peripheral Blood

Vessel Disease (PVD) and Diabetic Sores. The angiopumps developed at Epigenesis induce in the body a whole network of blood vessels. These help restore the blood flow to tissues, which have become ischemic due to poor circulation. The angiopump technology has vast implications in the cardiovascular field. The uniqueness of Epigenesis' cell-therapy approach is the secretion of whole repertoire of angiogenic factors by implantable angiopumps. This approach is in strong contrast to current competitor's approaches, which aim at providing only one angiogenic factor using gene therapy.  Epigenesis entered into a strategic  partnership with Teva Pharmaceuticals Ltd. in order to co-develop the aLIVE product all the way to market. Epigenesis plans to launch the aLIVE human pilot trial by middle of 2002.

 

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Multi-fold expansion of hemopoietic stem cells with minimaldifferentiation

GAMIDA CELL is a Biotech company developing bio-pharmaceutical products, based on its proprietary stem cell expansion

technology. GAMIDA CELL's proprietary technology enables multi-fold expansion of hemopoietic stem cells with minimal differentiation. GAMIDA CELL's first line of products addresses bone marrow transplant indications. The products will replace the

current sources of bone marrow, with effective cord blood based transplant. GAMIDA CELL's technology also enables the company to develop a biopharmaceutical business model, and provide to transplanters readily available, cost effective "cell drug"

products. GAMIDA CELL has finalized the pre-clinical development of StemEx, the company's first product for treatment of myeloablative  conditions. GAMIDA CELL is starting its clinical program this year in leading transplantation centers in the US.

Based on its proprietary technology, GAMIDA CELL is also pursuing a wide international program of cooperative work with other

biopharmaceutical companies, cord blood banks and academic institutions.

 

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New gene transfection agent for gene therapy

POLYGENE LTD. is a dynamic biopharmaceutical company focusing on the development of innovative polymer-based drug therapies. POLYGENE's proprietary biodegradable polymeric systems for targeted gene, peptide and drug delivery are addressing the complex challenges of improving the safety and efficacy of drug therapy. POLYGENE, founded in 2000, is applying the tools of biopolymer chemistry to the development of sophisticated proprietary drug delivery systems for small drug molecules, peptides and proteins, and therapeutic DNA genes. POLYGENE is currently developing three products: 1. PolyFectin- gene transfection agent for gene therapy, 2. Solid-tumor Biodegradable Polymer implant. and 3. Stereocomplexes for peptide and protein delivery.

PolyFectin is a water soluble biodegradable cationic polymer effective in transfecting therapeutic genes into cells. The solid

tumor implant is a solid polymeric implant made of a proprietary biodegradable polymer matrix loaded with an anticancer drug for

the treatment of solid tumors. These technologies are protected by five international patent applications (one issued in the US).

POLYGENE's mission is to become a leading company in the field of invasive controlled drug and gene delivery technologies and

products.

 

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Multi-Gene Vascular Systems

M.G.V. SYSTEMS LTD. - Multi-Gene Vascular Systems, develops innovative autologous somatic cell therapy products to address a number of vascular-related disorders in a variety of disease areas. The Company's patent-pending therapies utilize multiple

genes in conjunction with the patient's own (autologous) endothelial and smooth muscle cells. MGVS currently has three products at various stages in its pipeline, all based on the same technology platform: 1) multi-gene and multi-cell angiogenesis therapy for patients with arterial obstructive diseases; 2) multi-gene therapy to create bio-engineered grafts for use in peripheral vascular disease and end-stage renal disease (dialysis access site) and additional cardiovascular disorders; and 3) multi-gene and multi-cell angiogenesis and liver regeneration therapy for patients with liver cirrhosis, in conjunction with Cytonet GmbH& Co., a leading German cell therapy company. In addition to its cooperative efforts with Cytonet, the Company has also entered into several licensing agreements for specific genes and viral vectors. The Company's technology is already in advanced pre-clinical studies for both its angiogenesis therapies and bio-engineered grafts, both of which have shown highly promising results. MGVS will hold a pre-IND meeting with the U.S. Food and Drug Administration in November 2002, with the aim of beginning Phase I clinical trials for its bio-engineered graft during Q2 2003. The Company plans to commence Phase I clinical trials for its angiogenesis therapies by year-end 2003.

 

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Development of oncolytic viruses intended for cancer therapy

OVCure (Israel) Ltd. is a biotech start-up company focused on the development of viruses intended to cure cancer. OVCure’s first oncolytic virus product, OVC01 (formerly NDV HUJ), is in a Phase I/II clinical trial in patients with recurrent glioblastoma brain cancer. Oncolytic virotherapy is a rapidly emerging therapeutic area with the potential to complement chemotherapy and radiotherapy. OVC01 is a non-engineered, selectively replicative, strain of avian paramyxovirus type-1, an attenuated form of the virus that causes Newcastle Disease in poultry, but does not seriously affect humans. It is one of the few oncolytic viruses that can be administered intravenously. The virus is expected to be active against a wide range of cancers. NDV HUJ was first isolated by Prof. Zichria Zakay-Rones in the Virology Department of the Hebrew University Jerusalem. OVCure's development program has been greatly enhanced by its close proximity the Goldyne Savad Institute for Gene Therapy at Hadassah University Hospital  and its Phase I/II Outpatient Clinic and its National Facility for Clinical Grade Vector Production. As OVCure expands its development program it is interested in further outsourcing of pre-clinical testing, cGMP production of live virus vaccine, viral characterization and safety testing.

 

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Unique vectors for gene therapy constructed in the test tube from purified components of a pseudo-virus

GENE VECTOR TECHNOLOGY LTD. (GVT) has developed gene delivery system involving a new vector for gene therapy. The technology is based on the characteristics of viruses as natural carriers of genetic material to organism cells. By making particular

alterations to the virus it may be made to perform specific desired functions in carrying genetic material to cells, e.g., to restore damaged cells. Virus capsules are used as DNA packaging. Today various technologies utilize viruses as carriers to tissue

cells in the body. The proposed technology utilizes the viral vector SV40 and its preparation in a test tube from controlled

composites, yielding a pseudo-virus for use as a vector for gene therapy. The procedure that is carried out in the test tube will

be more efficient and better controlled than if it was carried out in a cell culture. GVT's unique vector combines the efficiency of a viral vector with the safety of a non-viral vector.

 

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Novel therapy for atrial fibrillation based on Gene Therapy

GeneGrafts is a new biotechnology company, developing a novel therapy for atrial fibrillation (AF). Atrial fibrillation is the most common cardiac arrhythmia affecting 2 million Americans. Conventional therapy for AF is based on medications taken daily,

with significant side effects. GeneGrafts is developing a transkaryotic approach using autologous (extracted from the patient) genetically modified cells that are delivered to the patient's heart by catheterization. The treatment is localized and involves a single procedure.

 

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Cell therapies and other treatment strategies for neurological, ophthalmologic and immune-related disorders

PRONEURON BIOTECHNOLOGY LTD. is the first company to harness the power of the body's own immune system for the treatment of debilitating central nervous system (CNS) disorders. The Company was founded in 1996 based upon the groundbreaking research of Professor Michal Schwartz, who demonstrated the role of immune response in normal and pathological conditions in the CNS. Proneuron is establishing itself as a fully integrated company that will independently develop and commercialize therapies for niche CNS disorders. Proneuron is currently focusing its expertise in cell therapy and neuroimmunology on the development and commercialization of a treatment for spinal cord injuries (SCI) as well as other neurological disorders, which until now were considered incurable. Proneuron's multithread business approach - a fully integrated niche CNS company and a source for product licensing for large pharma/biotech players, creates a wealth of potential revenue sources as well as a balanced risk profile. By developing the first potential therapy for the treatment of complete SCI patients that is expected to fundamentally improve the patients' quality of life and to significantly reduce the direct medical costs, Proneuron believes that this lucrative value proposition presents an attractive market opportunity. Proneuron has recently completed an FDA-approved Phase 1 clinical trial for this treatment, showing promising results and is now preparing for the next advanced stages of its clinical development plan. Proneuron has a 17,000 square foot R&D facility in Rehovot, Israel, in which its R&D activities are conducted. The Company currently employs 36 professionals, including 15 PhDs, MDs and veterinarians led by an experienced management team.

 

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Expanding human umbilical cord blood banks

HADASIT Medical Research and AGAM ETGARIM GROUP, a medical technology development company specializing in genetics and oncology, established GENCORD LTD., a company for the commercialization and expansion of the Cord uses. Cord Blood (CB) Transplantation is a very new procedure. Its advantage over "traditional" bone marrow transplantation is that cord blood is

extremely rich in the cells responsible for the formation of blood cells (hematopoietic cells). These cells develop into all types of blood cells and thus regenerate the entire bone marrow. GENCORD LTD. specializes in expanding human umbilical cord blood

banks to meet the increasing worldwide demand for cord blood for transplantation and cord blood products for use in cell therapy. The use of CB as a source of transplantable stem cells is increasing rapidly and great effort is invested in establishing

banks where CB from volunteer donors can be stored for transplantation. The company plans to: * Develop and validate a cord blood bank to become a worldwide leader in supplying cord blood for matching users. * Establish a private cord blood bank to provide health insurance for self-donors of cord blood. * Research and develop therapeutic tools by using cord blood and cord blood products. * Develop the use of cord blood as the ultimate factor for cell therapy.

 

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Development of gene delivery tools and anti atherosclerotic agents to better address cancer and cardiovascular diseases

VASCULAR BIOGENICS LTD. (VBL), a merger of Cardimmune and Medicard, develops innovative solutions targeting the vascular

wall. VBL is active in the field of Vascular Biology and develops innovative therapies to address significant current treatment

gaps in Cancer and Cardiovascular diseases. Based on a deep understanding of the biological processes that occur within the vessels, VBL is well-positioned today, to provide the causal and disease-modifying medicines of tomorrow. VBL develops technology platforms that address the cause of the disease rather than its symptoms. The Company's research and activity are divided in 2 Strategic Business Units (SBU) gathered around Atherosclerosis and Targeted Gene Therapy. In each SBU, the Company is currently conducting Pre Clinical studies, and schedules first clinical trials in 2003-2004. VBL owns a broad pipeline, including interesting proprietary peptides proven to be active against atherosclerosis; the Company believes that its pipeline will be leveraged by the time its first lead will get clinical validation. VBL owns 11 patent applications (from PCT to National Phase stage) and intends to build a strong and comprehensive IP portfolio that will allow for multiple exit opportunities. VBL business vision is based on building a strong patent position, allowing for multiple exit levels and broad collaborative network. VBL model is to bring some selected lead candidates to advanced proof of efficacy in human while developing a strong growing pipeline aimed at earlier strategic partnerships.

 

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Novel tools for research in molecular biology and medicine

GENE BIO-APPLICATION LTD., GeBA, develops novel tools for research in molecular biology and medicine. The company was

founded in May 1999 by Yitzhak Ben-Asouli and Farhat Osman, highly qualified Doctors in Molecular Biology from Hadassa

Medical School, Hebrew University, Jerusalem. GeBA `s first product: GeBAflex-tube, Gel Extraction & Dialysis kit, was completed in December 2001. GeBAflex-tube patent protected unit is able to extract any biologic macromolecule from any gel matrix and to dialyze small volume samples. This bio lab consumer product is recognized as a serious challenger to worldwide well-established competitors. GeBAflex-tube is produced at the GeBA plant as a complete kit for macromolecule extraction and dialysis process. The product has attracted over 20 distributors from New Zealand to the USA and 2 OEMs of worldwide reputation. GeBA's second project: Automated Plasmid Constructor (APC) for high throughput cloning is destined to reduce cloning operations

from present typical duration of several months down to few hours. The "Automated Plasmid Constructor" can effectively

combine several DNA fragments and ensure their correct orientation. Engineering of vectors will be straightforward and easy using Orientation Enrichment Reaction (OER), a breakthrough automated technology in constructing plasmid for high throughput

cloning. OER is GeBA patent pending reaction. In addition, a major benefit of this novel reaction is the ability to manipulate DNA sequences, to construct any kind of mutation (point mutation, deletions, insertions and others) as needed, in one single step

within a very short time. The whole process is completed by the APC using the OER. The user provides only primers and the DNA

template. The first prototype is able to construct four different genetic constructs in just five hours. The APC contains disposable parts to eliminate any cross-contamination (DNA templates, PCR products or PCR primers) during the process. Moreover, the APC serves as a "mini-laboratory" performing several independent processes, such as PCR, DNA fragment extraction from gels, gel analysis of the size and quantity of DNA or RNA fragments, and image processing. It is also possible to carry out two or more of these processes jointly and automatically. The APC harbors a partly disposable detection and fragment extraction (DFE) unit (GeBA developed), which provides the biologic processing capacity, OER, to be fully automated; the aim of the unit is to detect and extract the precisely wanted DNA fragment from the separating matrix. The DFE unit consists of hardware and software that control the operating of the DFE unit; analyzing the gel images, detecting and extracting the desirable DNA fragment from the gel. The software (GeBA developed) runs under Windows. The need for such a robot is very important. In research, the bottleneck of almost any molecular or cell biology research is the construction of new vectors. In the future, gene therapy will be a major tool used in the medical community. The biotechnology industry (medicine and agriculture) will use more and more genetically engineered organisms to produce new lines of products. The GeBA-APC is a fully functional operating system and provides

cloning services to GeBA customers in the world. GeBA is now looking for ONE major strategic partner who will invest capital for unit design and industrialization and worldwide support of qualified engineers network.

 

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Laboratory kit for measuring genetic expression

The kit determines the extent of expression of families of genes (on the level of mRNA). The testing kit is integrated with a

statistical program (in addition, according to customer request) that allows for unique analysis of the genetic components of a

cell and their comparison to other cells. The whole kit represents a particular family of genes, and contains test tubes, each of which has a combination of a pair of primaries suitable for particular areas reserved by the family of genes. The quantity of primaries in the kit enables repetition of the tests in 40 different conditions. The research program is written in VISUAL BASIC, DBASE and is supported by WINDOWS 95. The developed kits are principally suited for scientific use, in clinical and scientific research in fields such as molecular biology, genetic engineering and drug development - gene therapy. Every scientist interested in the determination of genotype of cells, whether `engineer' or an examiner of various materials on the genes, may utilize these kits. These kits supply differential information, and are easy to use. They do not require additional equipment, apart from the PCR item. The suitable market consists of agricultural researchers, researchers in clinical laboratories, various diagnostic laboratories

including quality testing and toxicology, and thus pharmaceutical companies involved in development. The novelty lies in the focus of the work, on the framework of particular gene families and the use of primaries from reserved areas of such genes to determine the level of expression of the genes. In a few reactions it is possible to cover a pattern of expression of a whole family of genes, to receive a realistic picture relating to all genes pertaining to the family that is expressed in the tissue, and thus work on organisms whose genotype is not determined.

 

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In the News

What is Gene Therapy?

Humans have some 35,000-40,000 genes each. A defect in virtually any one can lead to disease. Human gene therapy involves inserting a repaired gene into the DNA of a patient to replace a missing or defective gene. Currently there are more than 20 gene therapy research groups at Hadassah, more than any other medical center in the region. Day by day, experiment by experiment at Hadassah, we get closer to a time when doctors can anticipate and treat the root cause of illness, rather than merely struggle to keep up with its symptoms. Hadassah's institute is a comprehensive center -- where research laboratories, a goods manufacturing facility, and a clinical center for adult and pediatric patients are all under one roof in the Children's Pavilion at Hadassah Medical Center in Jerusalem's Ein Kerem. Since patients beds are side-by-side with labs, we can actually tailor the best program suited to their needs. In the coming decade, it is foreseen that molecular therapy in general and gene therapy in particular will be used to treat patients on an individual basis. Hadassah has chosen to take the lead in Israel's thrust into this new arena of medicine.

Israel In the Gene Era by Wendy Elliman

 

It has been 40 years since research into gene therapy began, and nine since the first repaired human genes were transferred into the first human patients. In that time, over 2,000 people have received gene therapy, 30 gene therapy companies have been established worldwide, and more than 200 gene therapy protocols, or treatments, havereceived FDA approval. But these figures can mislead. While many who have received gene therapy have been significantly helped, none has been permanently cured. A worldwide biomedical effort is now underway to make gene therapy viable, and Israel, with its treasure-house of ethnic groups, is an important player.

- There's no doubt gene therapy will work.- says Dr. Michal Roll, Research and Development  director at the Hadassah-Hebrew University Medical Center in Jerusalem. -The ideas are there. As we unravel more of the basic biology, we'll learn to construct healthy genes, get them to the right place, keep them there, get them working and, if necessary, shut them off. Early optimism that this would be simple, however, has long since faded. Finding genes and their faults has been likened by Dr. Francis Collins of the NIH to -searching for a burned-out light bulb in a house somewhere between the East and West coasts of North America, without knowing the state; much less the town or street the house is on.

- And that's only the first hurdle. Nature throws up highly effective biological blocks to the critical second stage: getting healthy gene snippets to a precise target cell or organ, where they must work in the right way. Scaling these hurdles is a worldwide endeavor, spurred by the Human Genome Project, the monumental $3-billion 15-year effort launched by the US in 1989 to find, identify and decipher the structure of each of our tens of thousands of genes. It's an endeavor in which Israeli researchers are making a special contribution. -Israel's population constitutes a rich human laboratory for molecular geneticists, because it's far easier to trace genetic anomalies in inbred groups with homogenous pedigrees, such as Yemenite and Moroccan Jews, Druse and Arabs, - says Prof. Nadine Cohen-Elbaz, head of the Tamkin Molecular Human Genetics Research Facility at the Technion Institute of Technology in Haifa. One current Technion project is a joint venture with GENSET in Paris, analyzing human genes to find links with common diseases, aiming to develop drugs to cure them. Another is a study of genetic anomalies among Israel's Arab population, where first-cousin marriages are common and genetic diseases found in 40 percent of them. Even when a gene is identified, however, its defects are hard to find. A complex gene, like that responsible for cystic fibrosis, can go wrong in hundreds of different places (almost 400 so far, and still counting). In Israel's rich and varied gene-pool, researchers are tracking down faulty genes and seeing why they go wrong. Prof. Orly Reiner at the Weizmann Institute of Science in Rehovot, for example, has cloned and identified a gene responsible for lissencephaly, a severe mental retardation that occurs in one of every 30,000 live births. She is now examining the role played by this LIS1 gene and its biochemical pathways in the developing brain.

Not all mutations, however, carry the same risk. Cohen-Elbaz is leading a multidisciplinary study of degrees of risk associated with different misprints in the familial breast cancer gene. Targeting high-risk Israeli Ashkenazi women (among whom breast cancer is 50 percent more common than in Israeli Arab women) Cohen-Elbaz is working with oncologists, clinical geneticists, psychologists and epidemiologists, reviewing family medical histories, diet and lifestyle, aiming to build an effective prevention program.

Where prevention fails, the aim is cure, and a key to gene therapy cure is getting the repaired gene to the right place. -Genes can't be injected,- says Prof. Ariella Oppenheim of Hadassah's hematology department. -They need special delivery vehicles.

One of the more promising such vehicles is the virus (an organism that's spent millennia refining itself to do exactly what gene therapists want: insert itself into cells. To become gene therapy's delivery boys, however, viruses must be stripped of their harmful qualities. Oppenheim is working with a virus from monkey kidney cells (SV40), which has a special affinity with bone marrow. She's hoping to make it a harmless envelope for healthy genes to repair defects resulting in crippling blood disorders, such as sickle-cell anemia and thalassemia.The parvovirus family is the focus of Prof. Ernest Winocour of the Weizmann Institute and Dr. Joe Corsini and Prof. Jacov Tal of the Ben-Gurion University of the Negev's Joyce  and Irving Goldman Medical School. -Parvoviruses are animal viruses that force their way into a cell's chromosomes in specific places,- says Wincour. -Knowing where the gene-package goes will give physicians far greater control. We've uncovered the mechanism parvovirus MVM uses to zero on its target -- an exchange of signals with the   chromosome -- and managed to replicate those signals.

The delivery vehicles aren't yet ready, but scientists are working on what they'll carry. Dr. Riad Agbaria of the Ben-Gurion University of the Negev is developing a cancer protocol in collaboration with the NIH. The aim is to insert a gene that produces enzymes that combine with a non-toxic drug, to make it lethal to tumor cells. It's only a matter of time, it seems, before gene therapy fully arrives. When it comes, Israel will be ready with a $10 million National Center for Molecular Medicine and Gene Therapy, opened at Hadassah in November. In a nation with no NIH, Hadassah has created this core facility where ideas can be generated, evaluated and tested in the laboratory, then progress through animal studies into an FDA-level Good Manufacturing Practice lab, where gene-based medications are tailored to the needs of individual patients in a clinical center for adult and pediatric patients -- all under one roof. Clinical practice is not, however, the final chapter, says Center head, Prof. Eithan Galun. -New medications must flow on to further research and development. We must monitor every step. If the protocol works, we must know why. If it doesn't, why not. It's a different kind of medicine from knowing aspirin reduces pain and fever without needing to know why.

As this revolution in biomedicine picks up steam, Israel's contribution will help open new doors to easy and effective ways of preventing disease, to fast and accurate methods of diagnosis, to simple and successful treatments, and to permanent cures for the currently incurable.

 

Wendy Elliman is a freelance writer living in Jerusalem.

 

The Goldyne Savad Institute of Gene Therapy

Hadassah University Hospital, Kiryat Hadassah

POBox 12000, il-91120 Jerusalem, Israel

gtx@hadassah.org.il

 

Tel. 972-2-6778589

Fax. 972-2-6437712

 

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Intel Israel heralds chip breakthrough        

A team of Israeli researchers at Intel has achieved a breakthrough in chip development that promises to change the world of computing and telecommunications within 5 to 10 years. 

 

For the first time, the team succeeded in developing electro-optical chipsets based on silicon wafers capable of converting electronic signals to optic signals within the chip. They have the potential to be mass produced at the same cost as standard electronic chips. Currently, the manufacturing cost of an optical chip (which is not silicon based) runs into hundreds or even thousands of dollars.

 

According to Intel's assessment, the electro-optic chips developed during the past year and a half at the company's Jerusalem facility will replace the standard electronic chips used for communications between computer components, allowing this communication to be conducted at the speed of light - 10 times the current speed.

 

"Today, the fast processors operate at speeds of three gigahertz, but their surroundings still work at speeds of hundreds of megahertz and, therefore, don't succeed in exploiting their speeds," explained Amir Elstein, the co-CEO of Intel Israel and director of Intel's Jerusalem facility. "When the chips, the processor and the ports of the computer speak at the same speed, which will be about 10 gigahertz, the computer's capability will be totally different," he added.

 

The new development will also change the multi-leg appearance of today's chipsets. "There will still be several legs on each chip, but most of the information will be transfered via a single optic opening of one optic port," Elstein said.

 

An Intel press release explained how the new technology works: "Researchers split a beam of light into two separate beams as it passed through silicon, and then used a novel transistor-like device to hit one beam with an electric charge, inducing a `phase shift.' When the two beams of light are recombined, the phase shift induced between the two arms makes the light exiting the chip go on and off at over one gigahertz (one billion bits of data per second), 50 times faster than previously produced on silicon. This on and off pattern of light can be translated into the 1's and 0's needed to transmit data."

 

Patrick Gelsinger, senior vice president and chief technology officer at Intel, called this "a significant step toward building optical devices that move data around inside a computer at the speed of light. It is the kind of breakthrough that ripples across an industry over time, enabling other new devices and applications. It could help make the Internet run faster, build much faster high-performance computers and enable high bandwidth applications like ultra-high-definition displays or vision recognition systems."

 

Elstein said last week that the company has not yet completed planning the production of the new optical devices, but that Intel's Kiryat Gat plant may be involved. "This is the greatest R&D success. There is no need to build new factories - faster chips can be manufactured at lower cost, with the same production infrastructure used in existing facilities. We took a theoretical physical affect and, using existing infrastructure, moved it up to a level that was previously impossible to implement," Elstein added.          

 

By Oded Hermoni

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U.S. and Israeli nanotech researchers set sights on clean water

Israel's nanotechnology program got a significant boost recently, with the first meeting of stakeholders in the Nanotechnology Clean Water Initiative, ISRAEL21C reported. The Initiative - the result of combined efforts by Dr. Uri Sagman, Prof. Samuel Pohoryles and former Prime Minister Shimon Peres - has, for the first time, brought together major Israeli university researchers and global industry principals to work on nanotech-based solutions to the water shortage in the Middle East.

The one-day forum took place at the Weizmann Institute in Rehovot, and included researchers from Weizmann, the Technion, Bar-Ilan University, Ben-Gurion University and the Hebrew University, executives from Luna Innovations of Virginia, from the Canadian NanoBusiness Alliance and European consulting firm Cientifica, as well as from the Andreas Agricultural Development Trust, an arm of the Peres Center for Peace.

It is hoped that the Water Initiative will result in practical new knowledge that can reduce the cost of water desalination and purification. To begin, the current participants have focused on research projects that can improve existing processes (for example, conventional reverse osmosis), but also intend to strike out in search of new processes.

 

IsraelLine

http://www.mfa.gov.il/mfa/go.asp?MFAH0of50

 

 

 

 

Advertorials

Sigma-Aldrich Corp. conducts research and development

The company, a wholly owned subsidiary of Sigma-Aldrich Corp. conducts research and development, manufacture and distribution of a broad range of biochemical, organic and inorganic chemicals, immunochemicals, tissue culture and molecular biology reagents, diagnostic reagents and related products. In addition, the company distributes laboratory equipment and supplies for centrifugation, chromatography, electrophoresis, filtration and distillation as well as computer products and scientific books.

The Jerusalem facility (formerly Makor Chemicals) develops and manufactures fermentation products such as antibiotics, microbial toxins, lipo-polysaccharides, nucleic acids and polynucleotides; synthetic organic compounds such as purines, pyrimidines, sugars and derivatives, steroids, neuroactive compounds and plant growth stimulators; proteins and enzymes extracted from microbial, plant and animal sources, lectins and conjugates, glycoproteins involved in cell adhesion, growth and differentiation factors, signal transduction reagents and transcription factors for molecular biology research; lipids and their conjugates totaling more than 1,700 products.

SIGMA-ALDRICH ISRAEL LTD.

Mr. Moshe Rashi

General Manager

3 Menahem Plaut St., Park Rabin

Rehovot

ISRAEL, 76326

Telephone: 08-9484222; 02-5893666

Fax: 08-9484200

Email: mrashi@sigma.co.il

WEB site: http://www.sigmaaldrich.com

 

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Health-Invest: The New Dutch magazine for Life Sciences

Health-Invest is a new magazine with popular scientific articles about the newest developments in Life Sciences in The Netherlands: health, new medicine and food. The magazine also includes fashion, carrier and financial business. Health-Invest wil highlight various subjects through combining Life Sciences and Life Style. Attention wil go to  stormy developments in the medical sciences, for innovative medical research and company profiles, as wel as developments in the general health and prosperity of society. Health-Invest is a Dutch language, internationaal orientated magazine about health and prosperity made for a large audience: from starters in Life Sciences, to those interested in health-care, the food sector, students, and especcially investors and eveyone interested in his own health. The next issue of Health-Invest will come out in January 2004 and wil focus on:  Nanotechnology Nanotechnology is today seen as the most important industrial revolution of the 21st century. In the next 25 years an enormous market will develop for products made with the help of this technique. Besides the information technology the medical profession wil also profit from nanotechnology. Our body is made up of cells and a technology that works on that level is much beter suited for treating sick cells than the treatments now available. The Netherlands has in this area a very good starting position in order to become an important  partner in this enormous nanotechnology market.  Health-Invest will focus further on this issue.

For more information contact: www.health-invest.nl  E-mail: info@health-invest.nl

 

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Announcements

EOI's for the Sixth Framework

Tel Aviv university has published the EOI's for the Sixth Framework on the web, and invites interested partners from the Netherlands (academy and industry) to join the consortia being formed. Contact can be made directly with the coordinator of each group or with the EU liason Office at the address on the web site: EOI's for the Sixth Framework

 

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Publish your projects in the Life Sciences Project Bulletin

If you have projects in the fields of Nano Bio, Gene Discovery, Functional Genomics and you are looking for collaboration, investments, partners or simply just promotion you can send us your profile and we will publish them in this bulletin free of charge. This bulletin is sent to over 2300 people in the Life Science industry in The Netherlands, Israel and other European countries. It is read world wide on the Optin website.

The Life Sciences Project Bulletin is a comprehensive survey of Life Sciences Projects with new and innovative technologies from various fields. The Bulletin allows its readers to save time and money in the selection procedure for finding new projects. It gives them projects in an organized fashion and provides them with direct access to the projects.

 

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Previous Bulletins

To see the previous bulletins click on Projects at our web site http://www.optin.nl/ : Projects in the fields of nanotechnology, drug discovery, genomics, proteomics, metabolomics, tissue engineering, functional foods, protein design, drug delivery, vaccine design, cancer therapy, neurological disorders, medical diagnostics, molecular imaging, fermentation and many more. For more information about Life Sciences in Israel and in The Netherlands look at the our web site http://www.optin.nl/ , your portal to Israeli and Dutch biotechnology.

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