While there’s no denying that optogenetics is one stimulating piece of biotechnology, the double entendre of optogenetics being a ‘turn on‘ has now become fact. The lab of Martin Fussenegger at ETH Zurich’s Department of Biosystems in Basel, Switzerland has developed a synthetic optogenetic technology that allows for the blue Viagra® pill to be skipped by a blue light that induces penile erection in rats.
Sildenafil (Viagra) is a phosphodiesterase inhibitor that prevents the breakdown of cyclic guanosine monophosphate (cGMP), a universal secondary messenger. Previously, the Fussenegger group has experimented with using Viagra to create the first synthetic mammalian cGMP switch. This allowed them to use cGMP as inducer, where the high levels enabled by Viagra induced expression of the secreted alkaline phosphatase (SEAP) reporter protein.
The effect was accomplished using a cGMP receptor fused to the VP16 transactivation domain. This novel system allows for the control of blood SEAP levels in mice by using Viagra and demonstrates the possibility of drugs being used to adjust genetic therapies in mammalian cells and mice, while also enabling the creation of a biosensor system for cGMP.
In this report the group uses their cGMP knowledge and previous system to complement optogenetic technology and allow for induction of a rather different phenotype by relying on proteins that will only bind in the presence of blue light.
Here’s what went up:
- They developed an “erectile optogenetic stimulator (EROS)” that was transfected into the corpora cavernosa of male rats.
- EROS is a synthetic designer protein consisting of a blue light response element fused to a guanylate cyclase, which produces a surge of cGMP in response to blue light by inducing the cyclase.
- EROS allows for a decoupling of erections from the primary physiological pathways and ultimately allows for one to bypass or “short-circuit” physiology and directly induce an erection (and sometimes spontaneous ejaculation) with optogenetics.
- The group also used their previous cGMP biosensor to produce SEAP as a metric for the molecular success of EROS.
Fussenegger shares that “The system of an erection is very similar across all mammals. Injection of a gene construct should not be a barrier to potential users, as injections in the erectile tissue are already a standard treatment for erectile dysfunction these days. An artificially induced erection would satisfy a great need among patients suffering from erectile dysfunction. Several doctors have confirmed this to me. In addition, not all sufferers are allowed to take Viagra; for instance, those with known heart disease.” Ultimately, this represents a very novel application of optogenetic technology, which is no surprise given the Fussenegger lab’s past work into wireless cross-speices optogenetic mind control of gene expression in mice that is triggered by mental state in humans.
Go and see what optogenetics induces in you over at Angewandte Chemie, March 2015