Current in vivo gene therapy (GT) approaches are beginning to demonstrate significant clinical and safety limitations that may ultimately reduce their therapeutic utility. In particular, the potential for systemic toxicity due to the antigenicity of the gene transfer vector, the prospect of insertional mutagenesis/oncogenesis during gene transfer, and the possibility of germ line transfer of the transgene are issues raising concern. One promising alternative to gene therapy that mitigates these clinical and safety issues is gene-based cell therapy (GBCT), in which autologous cells are removed from a patient and modified ex vivo for a desired characteristic prior to reimplantation. By transferring the transgene ex vivo, many of the issues surrounding the in vivo use of the transfer vectors are reduced and issues surrounding germ line transfer can be practically eliminated…
BioProcessing Journal Posts
Singapore’s vision is to become a global hub for the biomedical sciences (BMS) with world-class capabilities ranging from basic and clinical research to manufacturing and healthcare delivery. This vision encompasses pharmaceuticals, biotechnology, medical technology, and healthcare services. Singapore’s BMS initiative was launched in June 2000 with the goal of developing the industry into a key pillar of Singapore’s economy. It is overseen by a Ministerial Committee chaired by Deputy Prime Minister Dr. Tony Tan and implemented by an executive committee led by Mr. Philip Yeo, who is chairman of the Agency for Science, Technology, and Research (A*STAR) and co-chairman of Singapore’s Economic Development Board (EDB)…
The last decade witnessed remarkable scientific and technological advances in a number of scientific disciplines, including cell biology, microbiology, molecular biology, oncology, virology, infectious diseases, diagnostic technologies, analytical chemistry, instrumentation, and informatics. These advances have had a major impact on medicine, which has experienced fantastic progress in improving disease diagnosis, treatment, and overall patient care. Despite the advances in developing ever more sophisticated technologies and increasing the understanding of disease, new maladies continue to emerge. This is especially true for infectious ailments. Despite great developments in epidemiology, diagnostics, and agent detection technologies, as well as a comprehensive understanding of the biology of many known infectious agents and their virulence factors, we also are witnessing a dramatic increase in the number of new agents and diseases….
The globalization and sustained growth of the biotechnology market has brought the issue of biological packaging to the fore, particularly for those companies invested in cell and tissue bioproducts, such as engineered tissues and cells used for cell therapy. Biological packaging can be defined as the sum total of the physical device, temperature regulating and monitoring systems, type of preservation solution, and storage protocol(s) necessary to maintain cells or tissues in a “state of suspended animation” during transport or storage. The ideal biological package provides for the transport of cells and tissues throughout the global marketplace while maintaining both the viability and the function of the biological system at levels equivalent to those measured prior to shipment. Cells and tissues are currently shipped and stored under hypothermic (4–8ºC) or cryopreserved (–80 to –196ºC) conditions. These two processes have remained relatively unchanged over the past several decades, limiting their utility in the storage of modern bioproducts. However, recent evolutions in biological packaging have begun to provide scientific and financial benefits to researchers, clinicians, and corporate entities…
The human protein kinase superfamily is one of the largest and most important families of enzymes. More than 500 distinct kinases, classified in about 20 families on the basis of their primary structure similarity, have been identified to date. Protein kinases regulate a variety of biochemical pathways in cells through phosphotransfer reactions, playing pivotal roles in most signaling and regulatory processes, such as gene expression, proliferation, cell motility, and angiogenesis. Deregulation and/or mutational modification of protein kinase activity, leading to aberrant protein phosphorylation, is implicated in a variety of diseases, particularly cancer, making protein kinases important drug targets. A number of specific protein kinase inhibitors has been developed recently and more than 30 compounds are currently in clinical development or on the market. Many of these inhibitors are small-molecule compounds that compete with ATP for the highly conserved ATP binding site of the kinases. The development of highly selective and potent ATP-competitive inhibitors is driven by structure-activity relationship (SAR) studies, with X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy playing an important role in the understanding of the mechanism of inhibitor binding to the active or inactive forms of protein kinases…
One of the biggest challenges in the production of recombinant therapeutic proteins, monoclonal antibodies, and vaccines is the clarification and separation of the product (typically a protein) from the cell culture or fermentation broth. The desired product is present in low concentrations and must be efficiently separated from the other components present in the bioreactor fluid. An overall objective in developing a clarification process is to achieve the highest level of product recovery (yield) and contaminant removal with the fewest number of unit processes. Understanding how each operational step affects the performance of the next step downstream is the challenge at hand. Centrifugation, in combination with depth filtration, is gaining acceptance as the preferred method for the removal of cells, cell debris, colloids, insoluble precipitants, aggregates, and other materials found in mammalian cell culture and bacterial fermentation fluids…
Within the biopharmaceutical industry, mammalian cell culture is extensively used to manufacture a various biopharmaceutics uncluding antibodies, interferons, hormones, crythropoietin, clotting factors, immunoadhesins, and vaccines. The market for monoclonal antibodies (MAbs) alone is expected to grow 30% a year and reach sales of nearly $6.5 billion in 2004. The vast majority of these biotherapeutics are secreted glycoproteins obtained from mammalian cell lines such as: Chinese hamster ovary (CHO), human embryonic kidney 293 (HEK-293 or 293). NS0, and baby hamster kidney (BHK). As is the goal with most commercial products, biotechnologists strive to generate these valuable proteins in the highest yields possible in order to utilize mammalian bioreactor facilities efficiently…
Process development is an investment. As with a personal retirement plan, the importance of making the investment is not in question, yet strategies for when, how much, and where to invest in process development vary significantly from company to company. For a personal retirement plan, the answers to these questions are straightforward: invest as early as you can and as much as you can, and take less risk the closer you get to retirement. This would also be sound advice for investing in process development (substituting “BLA filing” for “retirement”) were it not for two complicating factors. First, the majority of biotherapeutics that enter the clinic fail to make it to the market. This makes a large, early investment in process development less attractive. Second, there is extreme pressure to get into the clinic, and subsequently onto the market, as quickly as possible, minimizing the time available for process development…
The biopharmaceutical manufacturing sector is rapidly gearing up production capacity to satisfy the steadily escalating global demand for complex biologics to combat a number of treatable illnesses. Frequently, the biotherapeutics in demand are too complicated to be chemically synthesized and thus are beyond the reach of traditional pharmaceutical approaches. To effectively address this issue, these products must be developed and produced using viable and robust biological systems…