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Biotechnology Process Engineering Center (BPEC) Making advances in the knowledge-base and technology-base aimed at overcoming crucial "bottlenecks" of nucleic acid therapeutics More information is available at web.mit.edu/bpec National Science Foundation (NSF)-Engineering Research Centers (ERC), Engineering Research Center Massachusetts Institute of Technology The MIT Biotechnology Process Engineering Center (BPEC) is a world leader in the training of students in biotechnology. BPEC emphasizes a fundamental but interdisciplinary approach to integrating molecular and cell biology with process engineering, with the simultaneous goals of creating advanced biological technologies, focusing on protein and nucleic acid therapeutics, and preparing top-quality individuals for leadership in this industry. BPEC now features two major thrust areas: Therapeutic Gene Biotechnology and Therapeutic Protein Biotechnology. Research The BPEC is moving its primary research direction from therapeutic protein biotechnology to therapeutic gene biotechnology, in order to attack bottleneck problems in this highly promising new area using the multidisciplinary approach proven in the Center's early years. The Center continues to maintain its emphasis on solving fundamental problems of generic importance for aiding the growth of a nascent industry. It is widely recognized that, at the present time, the crucial bottleneck holding gene therapy back from reliable implementation lies predominantly in the area of delivery. In particular, effective delivery of a therapeutic transgene is typically limited by one or more of the following issues, depending on the approach and application: (1) longevity, or repeatability, of transgene expression; (2) selectivity of transgene expression; (3) efficiency of transgene expression; (4) regulation of transgene expression. Our new BPEC program is dedicated to creating new fundamental knowledge, enabling technology, and a systems perspective addressing these issues in focused manner, synergistically combining bio/chemical engineering with molecular cell biology. Recognizing that different applications will require differing delivery vehicles, we are currently focusing our research efforts on two chief approach categories motivated by the issues listed above representing ex vivo and in vivo approaches, respectively. One approach category is the use of pluripotent stem cells transfected via chromosomal-integrating retroviral vectors, as an ex vivo gene delivery vehicle that can potentially offer expression longevity. Critical problems for this approach are expanding these cells to significant numbers in culture, and obtaining high transfection efficiencies for reimplantation. The second approach category is the use of nonviral targeted polyplexes as an in vivo gene delivery vehicle that can potentially offer expression selectivity and repeatable retransfection. A critical problem for this approach is transfecting cells with adequate efficiency. In both of these two approaches ex vivo stem cell delivery and in vivo targeted polyplex delivery a capability for regulating transgene expression at the tissue level using small molecule drugs is needed. We are therefore pursuing research directed toward this capability in relation to both delivery approaches. As ultimate aims we are focusing on hematopoietic stem cell gene therapy via retroviral vehicles as an ex vivo target application and on liver gene therapy via molecular conjugate vehicles as an in vivo target application. Accordingly, a centerpiece of our efforts is the development of tissue-engineered "vascularized" hematopoietic and liver cell microarrays to serve as a unique model testbed integrating all research projects. Our efforts in the area of production and delivery of therapeutic proteins also continue vigorously. Directions of current emphasis include protein folding and glycosylation, formulation issues for protein stability, novel delivery technologies, and protein engineering for enhanced potency. Industrial and Continual Education To ensure that the educational needs of industry are met, the BPEC provides one-week special summer courses. These one-week courses provide training on such topics as Fermentation Technology; Biotechnology; Principles and Processing; Modeling, Simulation, and Optimization; and Downstream Processing. Industrial Collaboration/Technology Transfer The industrial activities and planning are achieved through the Industrial Consortium Advisory Board. Research collaborations and technology transfer are achieved through the Center's Industrial Consortia. Direct industrial collaborations involve BPEC's students, research staff, and faculty. These collaborative efforts involve the Center personnel working directly with companies either at the Center or at the industrial sites. Transfer of technology and information is also routinely accomplished through several other avenues, including publications, participation in thesis committees, retreats, presentations, seminars, and theses. Keywords: Biological sciences-Cytology, genetics, and molecular biology; Medical Sciences and Technology-Biomedical technology Resource tags: Expertise; Funded university laboratories and centers
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