Abstract
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.
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