Instead of bioprocessing therapies the traditional way, Yuval Elani, PhD, UK Research and Innovation Future Leaders fellow and lecturer in chemical engineering at Imperial College London, and his colleagues create synthetic cells that can ultimately be used in the clinic. Elani says that these cells “are constructed from the bottom-up, often out of biomolecular components, to mimic the architectures and functions of living biological cells.” Despite the early stages of this work, Elani envisions many therapeutic applications.
“The ultimate goal is to design synthetic cells as smart agents that can sense a diseased site, activate themselves, migrate to the site of action, synthesize or release the drug, and then shut back down and re-circulate when the threat is eliminated,” Elani explains. In this way, artificial cells would deliver a drug to the intended site with limited off-target effects. Elani adds, “The potential for directional motility and propulsion paves the way for short- and long-range targeting.”
In Elani’s lab, he focuses on the membrane of these cells. “Beyond simply encapsulating cargo, the membrane is what gives them functionality,” he says. “For example, we design stimuli-responsive organelle membranes that sense external signals—light, heat, magnetic fields, presence of biomarkers—which then trigger actuation of the synthetic cell itself.” Plus, a cell’s design can include motility systems.
Using microfluidics, Elani controls the morphological and biophysical features of the cells. In addition, he says, “We make use of gene circuits, cell-free protein expression systems, and reconstitution of native cellular machinery—with the help of some fantastic collaborators—in many of the synthetic cells we design.”
Artificial cells offer huge therapeutic potential
Although this work is only at a proof-of-concept level, Elani says, “progress is rapid, and we and others are collaborating with clinicians to move things forward.” To turn this work into therapies, practical challenges need to be overcome, such as scaling up in an effective and affordable way to make the large quantities of artificial cells that would be needed for therapeutics.
In addition, the shelf-life and an artificial cell’s working life once administered must be addressed. “Currently, once activated, they run out of energy within a matter of hours, so people are developing a means for them to make their own energy so they can be self-sustaining.” Elani says. “In broader terms, there are public perception hurdles surrounding administration of designer cells as therapeutics, which shouldn’t be underestimated.”
Still, artificial cells offer huge therapeutic potential. They could yield the first truly smart therapeutics that seek out diseased states in the body, and specifically attack only it. Artificial cells “have the potential to be fully autonomous,” Elani says. “They can be programmed to make decisions on the fly in response to signals they encounter.” Those features have the potential to underpin the next generation of game-changing therapeutics, but only if the bioprocessing obstacles can be overcome.
For additional information on the Elani Group’s research, see “Dynamic Reconfiguration of Subcompartment Architectures in Artificial Cells” in ACS nano and “Interfacing living and synthetic cells as an emerging frontier in synthetic biology” in Angewandte Chemie International Edition.