Synthetic Cells: Rewriting the Rules of Biopharma Engineering

Key Takeaways

• Synthetic cells enable precise control over biological function, allowing developers to design systems for targeted protein production, drug delivery, and sensing applications.

• Bottom-up engineering approaches support customization and rapid iteration, accelerating development timelines compared to traditional cell-based systems.

• In biopharma, synthetic cells offer advantages in safety and efficiency, including reduced immunogenicity, elimination of replication risk, and minimized impurity generation.

• Therapeutic applications extend beyond delivery, with synthetic cells capable of on-demand protein expression, stimuli-responsive behavior, and localized treatment activation.

• Key challenges remain in scalability, functional integration, and biological complexity, requiring advances in engineering, manufacturing, and cross-disciplinary collaboration.

Defining what qualifies as a synthetic cell is not straightforward, as interpretations vary depending on context and application.¹ At its most basic, a synthetic cell can be described as an “artificial construct designed to mimic cellular functions.”² These constructs are not living cells, nor are they intended to fully replicate life. Because they are developed for diverse purposes, no single design or configuration serves as a universal model.³

Most synthetic cells are constructed as vesicles with an outer membrane — typically lipid-based, though sometimes polymeric — encapsulating an aqueous interior. Within this compartment, engineered components are assembled to reproduce selected aspects of cellular behavior. These may include artificial genomes, gene expression systems, information processing, signaling, metabolism, growth and division, motion, stimuli-responsive behaviors, and adaptability.^2–4

Despite these advances, synthetic cells remain far simpler than their biological counterparts. No artificial system has yet reproduced the full range of cellular functions. Instead, most are designed to perform a narrow set of tasks, often centered on a single capability.¹ One feature is universal: compartmentalization. The amphiphilic membrane separates the internal environment from external conditions, enabling controlled biochemical activity.³ The composition and structure of this membrane also influence key functions such as signaling, transport, and molecular interactions.

Synthetic cells can be constructed using three different strategies: top-down, middle-out, and bottum-up,³ The top-down approach involves using a modified genome from an existing organism. The middle-out or semi-synthetic approach combines known elements, such as organelles and components from cellular extracts, to form a synthetic cell. Most researchers use bottom-up engineering, which involves de novo creation of artificial cells from scratch via a step-by-step process. The membrane, DNA and other genetic materials, proteins, and other components are individually synthesized and combined to create the cellular system.

The bottom-up strategy is particularly attractive because it allows precise control over function through the deliberate selection of building blocks. Researchers can tailor both the internal machinery, such as genetic material and proteins, and the membrane composition to suit specific applications.² This approach also supports the incorporation of non-natural components, including synthetic amino acids, and enables unconventional uses of biological materials. For example, DNA-based cytoskeletal structures have been engineered using peptide–DNA assemblies that can be spatially organized within synthetic cells.⁶

Beyond enabling customization, bottom-up construction provides a platform for probing fundamental questions about cellular function. When used alongside top-down approaches, it can help isolate and evaluate the roles of individual cellular components.¹ More recently, researchers have also explored biohybrid systems, which combine living cells with synthetic elements to bridge the gap between fully artificial and biological systems.

Several methods are used to manufacture synthetic cells, including thin-film hydration, reverse emulsion, and electroemulsion.⁴ Increasingly, microfluidic technologies are being applied to improve the speed, reproducibility, and scalability of production. These systems enable techniques such as electroformation, extrusion, hydrodynamic focusing, pulsed jetting, transient membrane ejection, and octanol-assisted liposome assembly (OLA), among others. Synthetic cells produced using these methods typically range in size from approximately 0.5 microns to several tens of microns in diameter.

The advantages of synthetic cells depend on their intended application, but several overarching benefits are consistently recognized.⁴ Chief among these is their programmability and controllability. These features make synthetic cells useful for fundamental studies of cellular biology and the origins of life, as well as for applications in therapeutics, food production, and biomanufacturing.^2,3,5 Because they are not living systems, synthetic cells do not require the continuous input of energy and resources needed to sustain viability. Their internal machinery can instead be directed entirely toward a defined function, improving efficiency.¹

Synthetic cells may also simplify the development of cell-based therapies. By avoiding the need to engineer complex living cells, developers can design more streamlined and well-defined systems.⁴ This reduction in biological complexity can help mitigate risks associated with host–graft interactions and unintended immunogenic responses. In addition, synthetic cells do not replicate, which further reduces safety concerns related to uncontrolled proliferation.

At the same time, synthetic cells can exceed the capabilities of simpler delivery platforms. Their structural and functional complexity allows them to act as more versatile drug delivery systems than conventional nanoparticles, such as solid lipid nanoparticles (LNPs).⁴ They can also be engineered to perform functions that are not feasible in living cells, including the expression of proteins containing non-natural amino acids that would otherwise be toxic. These proteins may offer improved pharmacokinetic properties or novel mechanisms of action. Because synthetic systems do not rely on cellular replication, they eliminate the need for cloning, which can streamline design and production workflows.⁵

Advances in microfluidic manufacturing further expand their potential, enabling controlled, reproducible production that can support both personalized therapies and scalable manufacturing approaches.

Bottom-up approaches to synthetic cell design enable the construction of systems with specific, engineered functionalities, including material synthesis, information processing, spatiotemporal pattern formation, environmental responsiveness, autonomous movement, and adaptation.¹ These capabilities support a range of applications, from targeted therapies to protein production.⁴ In some cases, artificial cells have also been assembled into higher-order systems that mimic tissue-like behavior, including limited forms of intercellular communication.¹

Synthetic cells can be equipped with mechanisms that enable directed movement. For example, membranes functionalized with enzymes, complementary DNA oligomers, or light-activated protein binders allow these systems to migrate along chemical or physical gradients, a phenomenon referred to as localization.⁴ As with other drug delivery platforms, their surfaces can also be modified with ligands, such as antibodies, peptides, or small molecules, that bind selectively to receptors on target cells.

Many synthetic cells are designed with sense-and-response functionality. Membrane engineering enables responsiveness to a wide range of environmental stimuli, including temperature, pH, light, redox conditions, osmotic pressure, magnetic fields, acoustic signals, and enzymatic activity.⁴ These responses are typically mediated by stimuli-responsive molecules incorporated into or onto the membrane. In addition, membranes can be engineered with pores of defined sizes to regulate the transport of small molecules, such as signaling agents, nutrients, and chemical inducers, across the boundary.^3,4 Internally, components, such as transcription factors, RNA riboswitches, and enzymes, allow synthetic cells to process molecular inputs and generate defined outputs.

Protein expression represents a central capability for many synthetic cell systems.¹ Cell-free transcription and translation platforms are often encapsulated within artificial membranes to enable on-demand protein synthesis. This function underpins more complex behaviors, as it is required for processes such as replication and metabolism.

Some capabilities rely on native biological components, while others are introduced through non-biological design strategies.¹ For example, DNA and RNA origami approaches are being used to create functional architectures within artificial cells, avoiding the need for complex protein reconstitution.

Despite these advances, important limitations remain. Current synthetic cells can support bioproduction, sensing, information processing, and basic metabolic activity, but more advanced behaviors, such as growth, self-replication, evolution, and coordinated population-level control, have not yet been achieved.^1–3 Progress toward these capabilities will require integration of multiple functional modules. At present, most synthetic cells are optimized for a single function, and the conditions required for that function are often incompatible with others.

The use of artificial cells as alternatives to living cells for biomanufacturing is only in its infancy. However, the potential is significant, as the design and testing of synthetic cells can be achieved more rapidly.³ In addition, artificial cells can de designed to contain only the machinery necessary for expression of the desired product, eliminating unwanted side reactions and impurity generation to support higher titers and purities. Other benefits may include increased process control and resistance to biocontamination, contributing to improved safety profiles.

Beyond production, synthetic cell technologies are also being applied to downstream processing. Quintessence Biotech, for example, has developed a synthetic cell–based platform for the purification of cell therapies.⁷ Its DACS™ bioseparation technology uses proprietary biomimetic buoyant lipid droplets with artificial antigen-presenting cell (aAPC) characteristics to enable flotation-based separation. According to the company, this approach is simpler than conventional magnetic particle–based methods, improves efficiency and productivity, and can reduce cost of goods by up to 60%, while also enhancing therapeutic efficacy. Quintessence reports that the platform progressed from laboratory concept to functional production within twelve months and is currently being used in two customer-validated products expected to enter clinical trials in 2027.

Synthetic cells capable of producing bioactive molecules have clear potential as therapeutic agents. In this context, they function as advanced drug delivery systems with capabilities that extend beyond those of LNPs and other nanoparticle-based platforms. Their membrane composition and internal architecture can be precisely controlled, allowing them to be tailored to specific applications.⁸ Synthetic cells are also expected to exhibit greater stability than living cells and can be engineered to minimize immunogenicity.³

Encapsulation of in vitro transcription and translation (IVTT) systems within synthetic cells enables on-demand production of RNA, proteins, or small molecules. Combined with membrane modifications that support highly specific binding to target cells, these systems can achieve targeted delivery. Gene expression can also be regulated through embedded sense-and-response mechanisms, activating production only in the presence of defined environmental signals.^4˒8

Proof-of-concept studies highlight the range of possible therapeutic functions. Synthetic cells have been shown to synthesize anti-cancer proteins within tumor environments and to control the orientation of integral membrane proteins.⁴ In one example, synthetic cells incorporating magnetic nanoparticle cores surrounded by nucleic acids are guided into tissues using clinically tolerable magnetic fields. Localized heating generated through magnetic hyperthermia is then used to regulate protein synthesis and trigger payload release.⁹ Despite these advances, challenges remain, including low production titers, variability in post-translational modifications, and susceptibility to clearance and degradation within the body.⁴

Simpler therapeutic models are also being explored. In these cases, synthetic cells function primarily as carriers of pre-loaded drug payloads, similar to LNPs.⁹ However, they offer additional advantages, including improved tissue targeting and more controlled drug retention and release. For example, researchers have developed synthetic cells containing small-molecule payloads that respond to temperature changes.¹⁰ RNA thermometers regulate translation, triggering the synthesis of membrane pores that self-insert into the synthetic cell membrane and enable release of the encapsulated cargo.

Virtual Cells: Simulating Life at the Molecular Level

Progress in synthetic biology extends beyond physical constructs to include increasingly sophisticated virtual models of living cells. Recent work describes a simulation that incorporates all known chemical reactions occurring within a bacterial cell and models the process of cellular self-replication.^11,12

This simulation is based on the simplified organism JCVI-syn3A, derived by reducing the genome of Mycoplasma mycoides to fewer than 500 genes. The model captures the behavior of key cellular components, including DNA, proteins, ribosomes, and other macromolecules. To address gaps in current knowledge, genes with unknown functions were represented as inert spheres. In addition, the model restricts each messenger RNA (mRNA) molecule to a single ribosome, whereas multiple ribosomes typically bind to a single mRNA in living cells to produce several protein copies simultaneously.

Despite these simplifications, the simulation was able to reproduce many of the cellular dynamics observed in real biological systems, demonstrating the growing potential of virtual synthetic cells as tools for studying and designing complex cellular behaviors.

Continued advances in the design of synthetic cells and their component systems are expected in the coming years. The application of artificial intelligence and machine learning is likely to accelerate the development of cells with multiple, integrated functionalities, enabling more complex and coordinated behaviors.

Over time, increasingly advanced capabilities may be achieved. Some researchers anticipate that it will ultimately be possible to construct fully living cells from nonliving components.^1–3 Realizing this goal will require sustained progress across multiple fronts, particularly in integrating individual functional modules into cohesive systems.

Success will also depend on close collaboration among regulators, academic researchers, and biopharma industry experts. The field draws on a wide range of disciplines, including genomics and metabolomics, lipid and polymer chemistry, biomanufacturing, and drug development and formulation.⁵ Coordinated efforts across these areas will be essential to translate emerging advances into practical applications.

1. Adamala, Katarzna P, et al. “Present and future of synthetic cell development.” Nat. Rev. Mol. Cell Biol. 25: 162–167 (2024).

2. Giaveri, S., et al. “Building a Synthetic Cell Together.” Nat. Commun. 16: 7488 (2025).

3. Rothschild, Lynn J, et al. “Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities.” ACS Synth. Biol. 13: 974−997 (2024).

4. Sato, Wakana, et al. “Synthetic Cells in Biomedical Applications.” Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 14: e1761 (2021).

5. Sampson, Kira, Carlise Sorenson, and Katarzyna P Adamala. “Preparing for the future of precision medicine: synthetic cell drug regulation.” Synth. Biol. (Oxf). 9: ysae004 (2024).

6. Daly, ML, et al. “Designer peptide–DNA cytoskeletons regulate the function of synthetic cells.” Nat. Chem. 16: 1229–1239 (2024).

7. “Quintessance Biotech Unveils the First Living Artificial Cell for Millions of Patients Worldwide.” First World Pharma. 18 Mar. 2026.

8. Siquenique, Sónia, et al. “Bioengineering lipid-based synthetic cells for therapeutic protein delivery.” Trends in Biotechnology. 43: 348 (2025).

9. Parkes, E, et al. “Magnetic activation of spherical nucleic acids enables the remote control of synthetic cells.” Nat. Chem. 17: 1505–1513 (2025).

10. Monck, C, Y Elani, and F Ceroni. “Genetically programmed synthetic cells for thermo-responsive protein synthesis and cargo release.” Nat. Chem. Biol. 20: 1380–1386 (2024).

11. Callaway, Ewen. “‘Virtual cell’ captures the most-basic process of life: bacterial division.” Nature Briefing. 10 Mar. 2026.

12. Thornburg, Zane R., et al. “Bringing the genetically minimal cell to life on a computer in 4D.” Cell. 9 Mar. 2026.