A designer network coordinating bovine artificial insemination by ovulation-triggered release of implanted sperms

作者：Kemmer Christian; Fluri David Andreas; Witschi Ulrich; Passeraub Alain; Gutzwiller Andreas; Fussenegger Martin^*

来源：Journal of Controlled Release, 2011, 150(1): 23-29.

DOI：10.1016/j.jconrel.2010.11.016

• Cellulase
• Cellulose sulfate
• Synthetic biology
• Synthetic circuit

Synthetic biology has been successfully used to program novel metabolic function in mammalian cells and to design the first-generation of prosthetic networks that have shown the potential for the treatment of obesity, hormone-related disorders and hyperuricemia in small-animal model systems. By functionally rewiring luteinizing hormone receptor signaling to CREB1 (cAMP-responsive element binding protein 1)-mediated transgene expression via the common cyclic adenosine monophosphate (cAMP) second messenger pool we have designed an artificial insemination device which enables lutropin-triggered in-utero release of sperms protected inside cellulose-based implants. Swiss dairy cows treated with such in-utero implants containing spermatozoa and mammalian cells transgenic for luteinizing hormone receptor and CREB1-inducible expression of an engineered cellulase showed ovulation-triggered implant degradation and sperm release leading to successful fertilization of the animals. Synthetic devices plugged into endogenous control circuitry enable the body to automatically control spatio-temporal metabolic activities that could improve the economics of cattle breeding and provide novel opportunities for future therapeutic interventions.

• 出版日期2011-2-28