Expression of recombinant Hirudin in transgenic mice milk driven by the goat beta-casein promoter
Research article published in Biotechnol J (2008)
Abstract
Hirudin, isolated from the leech Hirudo medicinalis, inhibits thrombin directly and several expression systems have been used to produce recombinant Hirudin (rHirudin) for pharmaceutical purposes. A DNA fragment containing the Hirudin coding sequence and goat beta-casein secretion signal was chemically synthesized in this study. The synthetic DNA then was further constructed into a goat beta-casein expression vector for mouse transgenesis. Four lines of transgenic mice were successfully developed and one line showed a meaningful anti-thrombin activity of 40,000 anti-thrombin units (ATU)/mL in their milk. In this animal line, Hirudin mRNA was found in samples of uterus and kidney with insignificant anti-thrombin activity (</= 280 ATU/g wet tissue); however, mammary glands showed a higher activity of 780 ATU/g wet tissue. Transgenic mice showed no evident physical abnormality. The purified rHirudin was further analyzed by amino acid analysis and was found to contain a tyrosine O-sulfate residue that is absent in rHirudin expression either through Escherichia coli or yeast host systems. Experimental results demonstrated that the beta-casein-promoted Hirudin transgene could be successfully expressed in a murine model and may be applicable to large mammals such as livestock for mass production of rHirudin for pharmaceuticals.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Transgenic mice secreted recombinant hirudin in milk at 40000 anti-thrombin units/mL; purified rHirudin contained tyrosine O-sulfate residue absent in E.
Warum dies für die Hirudotherapie relevant ist
This study produced recombinant hirudin in the milk of transgenic mice using a chemically synthesized hirudin coding sequence with a goat beta-casein secretion signal, yielding one line expressing 40,000 anti-thrombin units (ATU)/mL in milk. Mammary gland tissue showed 780 ATU/g wet tissue while other organs had insignificant activity; purified rHirudin contained a tyrosine O-sulfate residue absent in E. coli- or yeast-expressed product, and transgenic mice showed no evident physical abnormality. For ASH, this is relevant as it addresses recombinant production of hirudin, a key leech-derived anticoagulant, with potential applicability to large mammals for pharmaceutical mass production. Caveat: This is a proof-of-concept transgenic animal biotechnology study; no pharmacological efficacy, safety, or clinical data beyond gross physical appearance are presented.
Zitation
Expression of recombinant Hirudin in transgenic mice milk driven by the goat beta-casein promoter.
Yen CH et al. · Biotechnol J, 2008
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