Modification of the Bovine Genome for the Large-Scale Production of Human Serum Albumin

There is a vast clinical need for human serum albumin (HSA) with nearly 500 metric tons used worldwide every year. As a major protein in the human body, HSA plays a vital role in many physiological processes including the maintenance of oncotic pressure and the transport of various biomolecules and pharmaceuticals. Currently, all HSA used for clinical blood expansion purposes is isolated from pooled human blood or plasma, an unpredictably fluctuating supply that can potentially fall to dangerously low levels. Furthermore, this supply is derived from thousands of different donors that could potentially result in the spread of pathogenic contaminants to recipients. One solution to the problem is the use of transgenic animals, such as cattle, as living bioreactors, enabling large-scale production of recombinant HSA (rHSA) in a cost-effective manner. Cattle are capable of producing large amounts of milk that can potentially yield large quantities of a desired recombinant protein. The production of rHSA in the milk of cattle would provide an economical resource that circumvents the current dependence on blood bank supplies. Previous bovine transgenics, which simply express ectopic rHSA in the milk, have not proved commercially viable. This is primarily due to the presence of endogenous bovine serum albumin (BSA) in the milk, a highly conserved ortholog of HSA, which necessitates a tedious and prohibitively expensive purification process. Our approach is to humanize the endogenous BSA gene, replacing it with an rHSA minigene construct, which should allow normal expression of rHSA protein in the liver as well as exogenous expression of rHSA in the milk.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2013

Author dc:creator

• Moghaddassi, Shaida

• Biotechnology

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/39133

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/39133