Artificial cells have great potential in changing precision medicine for the better. These are membrane-bound vesicles that contain specialized internal chemistry that gives them the ability to make and deliver a “payload” — a drug or method of biochemical treatment. They possess several unique properties that sets them apart from natural cells, expanding what’s possible in future artificial cell pharmaceuticals.
This field of research took off in late 1990s, when Craig Venter, founder of the J. Craig Venter Institute, engineered the first single-cell synthetic organism, which he called JCVI-syn1.0 — a mycoplasma with an engineered synthetic genome.
While synthetic cells mimic many properties of natural cells, they can be designed to only include the parts and pieces needed to serve a specific purpose. Being able to add desired organelles or components and remove what isn’t needed allows scientists to cater them to specific tasks. This comes in handy when a drug is needed to provide targeted treatment in the body. Artificial cells can travel to a precise location and deliver the drug, instead of “crop dusting” the whole body unnecessarily.
This ability is made possible through these cells’ specialized chemistries — molecules sensitive to light, magnetism, acoustics, redox states, and enzymes — which allow them to respond to certain biological signals. In the era of precision medicine, this sensitivity opens doors to drugs that respond and adapt to mutating diseases and the dynamic human body.
Beyond just drug delivery, synthetic cells are capable of their own gene expression and are thus able to produce RNAs, proteins, and small molecules on site. This might translate to a medicine that synthetizes anti-cancer proteins inside of tumors or drug molecules that kill toxic cells in the body, eliminating unwanted side effects of these treatments.
To transfer them from the lab to clinic will require extensive manufacturing and regulatory development.
Experimental hurdles remain
This technology is still in its early stages of development and effective sensors and transporters that can activate in response to specific stimuli and control molecules flowing in and out of the cell are still in the works. This machinery, of course, already exists in living cell membranes, such as those found in bacteria, but their size and complexity make translating them to their artificial counterparts challenging.
Stability is also a prevalent hurdle in the field. Living cells remain in the bloodstream for a very long time before they are broken down. The body’s natural functions constantly work to break down and eliminate foreign molecules, regardless of how helpful they might be. This was previously only possible with living cells, but advancements in the field are constantly bringing us closer to this goal.
Bringing all these moving parts together
Experimental challenges aside, perhaps one of the greatest obstacles in the field is making all of these developments and technologies compatible with one another. Scientists around the world are working to create innovative new ideas and engineering techniques, which have resulted in advancements such as enhanced genome engineering and building artificial membranes. However, in order to make a fully synthetic cell, these technologies will eventually have to be combined — a task that is proving to be more difficult than expected. Each subsystem is typically engineered with a scientist or team’s methodology, creating a diverse array of chemistries and structures to piece together to create a functional, working product.
The next step is manufacturing if synthetic cells are ever to be used in a clinical setting. Manufacturing each of these components and streamlining production processes is also quite expensive. One possible way to mitigate these costs is by scaling up existing infrastructure — scaling up existing cell-free protein expression systems to 100-liter reaction volumes has already been demonstrated, and if sufficient supplies of reagents can be obtained, synthetic cells can effectively be mass manufactured.
While cost and scalability are always significant obstacles to industry, as technologies expand, development and scale-up costs will decrease, and potentially be offset by increased profitability.
Synthetic cells don’t come without ethical concerns
As this is such a new field and the technologies are all so novel, gaining public awareness and policy support should be a priority. Synthetic cell technologies are so unique and novel that the FDA has yet to provide guidelines for synthetic cell drug products, making it impossible to deploy this technology into the pharmaceutical industry.
This is in part, due to the ambiguity existing around artificial cells. Scientists have yet to agree on exactly what synthetic cells are and what they’ll look like in the future. For example, how will regulations for living cells with synthetic genomes or others with synthetic organelles differ? Important regulatory evaluation rubrics, like those for biosafety level guidelines, haven’t yet been written to effectively evaluate synthetic biotechnology.
Without policy, we risk perpetuating both ethical and safety issues into society. If manufactured incorrectly, synthetic cells could malfunction, causing potential harm. Similarly, if leftover live cellular debris remains in synthetic cells, it may have toxic impact upon entering the human body. In order to safely implement them into the pharmaceutical industry, we’ll need both manufacturing and safety guidelines that drug developers must adhere to.
The first synthetic cell-based drug on the market will begin a new chapter, providing new opportunities to expand our capabilities in diagnostics and treatment; moving beyond just biomedical applications. Maximizing the impact of artificial cells requires that the field rapidly address safety, manufacturing, and cost concerns proactively.
Future looks bright
In the last few decades, synthetic biologists have made many strides and artificial cells’ potential in revolutionizing medicine has only grown. However, building dynamic systems, such as these, remains difficult. Creating a fully synthetic cell, in which all its components — from the membranes, organelles, intracellular fluid, and genome — are completely synthetic, has not yet been accomplished, but with each research paper published this dream inches closer to reality.
Written by: Kira Sampson, Carlise Sorenson, and Katarzyna Adamala
Reference: Wakana Sato, et al., Synthetic Cells in Biomedical Applications, WIREs Nanomedicine and Nanobiotechnology (2021). DOI: 10.1002/wnan.1761