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The Agreement with the Government on the Establishment of the NIBN REPORT The National Institute for Biotechnology in the Negev 5 February 2008 The agreement with the government on the establishment of the NIBN: On the threshold of a new era After months of negotiation with the Government, agreement on the establishment of the NIBN is just around the corner. Indeed, I hope this NIBN report will be the last one before the implementation of the agreement of the NIBN funding by the Government, our principal Donor and the University. Such an agreement will mark a turning point with respect to NIBN activities, the support of its members and the advancing of its goals. This issue of the NIBN report is also being published before the visit of the extended International Advisory Committee. I greatly look forward to this visit which is aimed at exploring the potential of the NIBN and to help us transform the NIBN into a world-class research center, both in terms of its people and its facilities. One of the challenges that the NIBN faces is bringing industry to the Negev. While it is crucial that NIBN members stand behind this goal, I admit that it is not easy to present a clear road-map of how to move forward on this front. There has always been a rather uneasy relationship between the interests of basic science and those of the business world. While biotechnology companies are product-driven, with focus on the immediate, namely developing a product to meet a specific market need, academy is discovery-driven and takes a long-term view of biotechnology development. Over the last months, I have had the opportunity to present the mission and goals of the NIBN to major players in industry and biotechnology, as well as to faculty forums at BGU. While the importance of exposing industrial concerns to the NIBN is obvious, I also believe it is very important to expose the BGU faculty to the NIBN mission, its structural organization, its research focuses and the relationship between the NIBN and the University. Moreover, I have made every effort to highlight the benefits to the university that will result from the establishment of the NIBN. These include the fact that the NIBN attracts and recruits excellent scientists, allowing them to develop their research as well as providing a collaborative research atmosphere as well as establishing industrial contacts. I believe that the exciting research going on in the NIBN will greatly benefit from the new links with industry that have been established but which are too numerous to list here. Finally, as in previous NIBN reports, in this issue we shine the spotlight on some of our members. We introduce you to Dr. Ran Taube, a newly-recruited scientist joining the NIBN and the HIV as a tool for gene delivery and discovery of new antibodies Dr. Ran Taube Gene therapy is broadly defined as the How can the genetic material get detect in other microbial or cellgfree transfer of genetic material into cells into cells? display systems. Moreover, we are curg rently collaborating with researchers and tissues, with the goal of either regg A basic approach for gene therapy ing at Harvard University in a pregclinig gaining or inhibiting the function of volves the use of viruses as genetic deg cal study, where we use viral particles a given gene. The approach is mainly livery vectors, capable of efficient and to introduce an intracellular antibody used to cure genetic disorders, or at stable gene transfer, without causing (intrabody) against the HIVg1 Tat prog least improve the clinical condition of any undesired associated pathogenic tein into Rhesus macaque monkeys, a patient. Researchers may use several or immunogenic effects. These engig and analyze the protective effects of techniques for correcting defective neered shuttle vehicles are safe and such intrabodies against viral infecg phenotypes, the most common being cannot replicate, but still maintain tion. to insert a functional gene into the geg their capabilities of delivering new In December, 2007, I joined the nome, where it replaces the nongfuncg genetic material. Both RNA and DNA NIBN and the Department of Virolg tional copy. Additionally, the regulag viruses can be used as shuttle vectors ogy and Developmental Genetics at tion (i.e. the degree to which a gene is for gene therapy manipulation. Such the Faculty of Health Sciences. I am turned on or off) of a particular gene vectors are based on wellgdefined retg certain that this environment will could also be altered. Other agents roviruses, like murine leukemia virus allow me to continue my research in that can inhibit a corrupted gene (MLV), or DNA viruses, such as adg Schematic diagram illustrating the assay for the screening a competitive manner, and to estabg include: RNAgbased drugs, such as enoviruses or adenogassociated virusg andisolation of scFv particles from mammalian cells. lish an independent scientific career, siRNA, dominant negative variants, es. Each vector has its own advantagg A diverse scFv non-immune library was inserted into a lentivector as a fusion protein of an Fc domain and a transmembrane moiety. Generated viral particles were used to transduce new cells, leading combining both basic and applied toxins, and intracellular antibodies. es, but all share a major shortcoming, to a stable integration of scFv fusion proteins in the host genome and their expression on the cell research. My group and I will cong Obviously, genetic disorders that arise namely they cannot infect (transduce) surface. The result is a collection of cells, each displaying scFv on the surface. For isolating cells tinue to improve the mammaliang from mutations in a single gene are nongdividing cells. To overcome this displaying specific scFv molecules, cells were sorted based on their binding to a fluorescent-labeled display screening system and isolate the best candidates for gene therapy. problem, novel retroviral vectors deg antigen. Sorted cells were expanded and re-selected or the scFv fragments were directly PCR-rescued new scFvFc particles directed against However, gene manipulation can also rived from lentiviruses g such as hug from the cells and re-cloned either into the lentivector for a second round of screening or directly into numerous infectious diseases. These be conducted to treat a broad range of man immunodeficiency virus (HIV) an expression vector. can be engineered into highly efficient metabolic and neurologic disorders, – have been developed. These novel agents that will be further utilized for different kinds of cancer, hemophilia, vectors promote high and stable exg caution. Clearly, further understandg chain antibodies (scFvFc), consisting therapeutic applications. We will fog cardiovascular disorders, and numerg pression of the transgene, and also ing of their mechanisms is essential of both the heavy and light variable cus our efforts on HIV targets, mainly ous infectious diseases. offer great advantage for longgterm for developing improved gene therapy regions of an antibody. These partig on viral proteins that participate in therapy, in that they efficiently infect technologies. cles, expressing scFvFc fragments on the regulation of transcription elongg embryonic stem cells. their surface, were used to deliver the gation. Additionally, we will continue Still, the ideal delivery vehicle still How can our lab promote the safe library into human cells, resulting in to develop improved and safer lentig remains to be found. At this time, the transfer of genetic material? stable scFvFc surface expression. This viral vectors. Our recombinant scFv performance and pathogenicity of In our lab, we set out to exploit lentivig unique mammalian display platform pseudogtyped lentiviral particles will candidate vectors, along with quesg ral particles as genegdelivery vehicles. for screening new scFvFc particles is be used as highly efficient gene delivg tions on safety and ethical parameters, Intracellular antibodies (intrabodies) required to overcome constraints asg ery vehicles to target specific cells via are being considered. Encouraging reg or other agents that can correct the sociated with protein expression and their scFv moiety, while maintaining sults have formed the basis for clinical function of the gene, are delivered into obstacles related to library size, corg their highly infectious properties. Fig trials addressing numerous disorders. cells for the treatment of infectious rect folding, and protein postg transg nally, our human display platform can However, despite some initial success diseases, mainly Human Immunodeg lational modifications – all of which accommodate other protein libraries in these trials, previous drawbacks ficiency Virus (HIV). In addition, we limit bacterialgdependent antibody that are currently screened in bacteg have halted our progress. Thus, presg use lentiviral vectors for the developg selection methods. Upon screening rial systems, allowing the isolation of ent viral vectors are used with great ment of a new display platform for the of these human cells by FACSgsort newly improved variants with unique screening of largegsized protein librarg technologies, improved scFv moieties structural and biochemical properg Cell-Surface localization of scFv ies in the context of mammalian cells. directed towards the envelope glycog ties. We hope to take these newly isog Cells were transfected with a bicistronic During my postgdoctoral training at protein of the SARS virus were isog lated agents a step further, and benefit vector expressing both the scFvFc-TM fusion the DanagFarber Cancer Institute at lated. Overall, we have
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