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At present, several recombinant human bone morphogenetic proteins (rhBMPs) can be produced in mammalian cells. If rhBMPs with a high activity could be produced in bacteria, the bacterial expression system is very useful in clinic. We examined in vivo serial changes in the bone inducing ability of an Escherichia coli-derived rhBMP-2 (ErhBMP-2) variant with N-terminal sequence. Five μg of ErhBMP-2 was mixed with 3 mg of atelopeptide type I collagen (CL) as the carrier, and specimens were implanted into calf muscle pouches of Wistar rats (n = 20). After 3, 7, 14 and 21 days, 5 specimens each were examined. New cartilage was observed 7 days after implantation of ErhBMP-2 with CL. Induced bone was found on the outermost edge of the implant after 14 days. After 21 days, bone formation was associated with much fatty marrow. ALP activity and calcium content gradually increased with time. These changes were similar to those in a study using Chinese hamster ovary cell-derived rhBMP-2. However, these increases were slightly higher than those in the rhBMP-2 study. From these findings, ErhBMP-2 appears to be completely renatured while maintaining its biological activity. ErhBMP-2 with CL may expand by absorbing body fluid in vivo to greater extent than rhBMP-2 with CL, because it lacks heparin-binding sites. A variant ErhBMP-2 showing high activity in vivo, obtained by the bacterial expression system is an important finding, as it should be possible to produce large quantities of ErhBMP-2 at a low-cost for clinical use, in the near future.

The Biotechnology Incubation Center of Academia Sinica: A Gateway to Innovative Taiwan.

Cancer Targeting Nanomedicine: An Opportunity for Drug Development in Asia with Emphasis on Taiwan.

Recombinant Lipoproteins for the Development of Novel Subunit Vaccines.

Discovery of Therapeutic Human Monoclonal Antibodies through B-cell Immortalization Technology.

The use of engineered antigen carriers to optimize the immune response to recombinant subunit vaccines has seen great advances in recent years. Optimization can take several forms, such as facilitating stimulation of certain immune cells or amplifying the adjuvancy effect of the vaccine formulation. In this paper, we applied dose/response analysis to demonstrate the ability of outer membrane vesicle (OMV) antigen carriers derived from engineered Escherichia coli to produce strong antigen-specific immune responses to a model antigen at a significantly decreased antigen load compared to an industry standard alum-based control. Inflammopathology and histological analysis of extended studies further supported a capacity to enhance immune cell recruitment locally at the injection site while decreasing inflammation and eliminating injection site scaring. The results indicate a strong potential for OMV-based vaccines as recombinant antigen delivery vehicles, affording strong immunogenicity at low doses with a broadly applicable platform for recombinant subunit antigen inclusion.

Collagen is the most abundant natural protein found in living systems. While there is a whole family of different collagen types, each differing in sequence, the properties that make this protein so attractive as the building blocks for medical devices, are reflected largely by the unique fibrillar structure of the molecule, as well as defined functional regions that interact with the surrounding cells and other matrix components. As a commercial medical product, collagen can be part of the natural tissue used in the device, or it can be fabricated as a reconstituted product from animal or recombinant sources. Both types of uses have distinct properties that convey advantages and disadvantages to the end product. This review examines the chemistry and biology of collagen and describes some well-documented examples of collagen-based medical devices produced in one or other of these formats.