Artificial cell
[3][4] The main advantages of encapsulation include improved mimicry in the body, increased solubility of the cargo and decreased immune responses.
Advances in cell-free transcription and translation reactions allow the expression of many genes as well as interdependent genetic and metabolic networks,[7] but these efforts are still far from producing a fully operational cell.
A bottom-up approach to build an artificial cell would involve creating a protocell de novo, entirely from non-living materials.
[9] In a similar way, functional biological building blocks can be encapsulated in these lipid compartments to achieve the synthesis of (however rudimentary) artificial cells.
[10][11] The main hurdles foreseen and encountered with this proposed protocell are the creation of a minimal synthetic DNA that holds all sufficient information for life, and the reproduction of non-genetic components that are integral in cell development such as molecular self-organization.
[12] However, it is hoped that this kind of bottom-up approach would provide insight into the fundamental questions of organizations at the cellular level and the origins of biological life.
So far, no completely artificial cell capable of self-reproduction has been synthesized using the molecules of life, and this objective is still in a distant future although various groups are currently working towards this goal.
[14] Protocell research has created controversy and opposing opinions, including critics of the vague definition of "artificial life".
[20] Build-a-Cell has conducted nine interdisciplinary workshopping events, open to all interested, to discuss and guide the future of the synthetic cell community.
[25] It is hoped that the process of top-down biosynthesis will enable the insertion of new genes that would perform profitable functions such as generation of hydrogen for fuel or capturing excess carbon dioxide in the atmosphere.
[28] As of 2016, Mycoplasma genitalium is the only organism used as a starting point for engineering a minimal cell, since it has the smallest known genome that can be cultivated under laboratory conditions; the wild-type variety has 482, and removing exactly 100 genes deemed non-essential resulted in a viable strain with improved growth rates.
[3] Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry microorganisms, vaccines, genes, drugs, hormones and peptides.
[39] This is done by having artificial cells express a pore forming protein - alpha hemolysin - under the control of an RNA thermometer, allowing for cargo release to be coupled to temperature changes.
The technology relies heavily on viral vectors which raises concerns about insertional mutagenesis and systemic immune response that have led to human deaths[47][48] and development of leukemia[49][50] in clinical trials.
[31] Activated charcoal has the capability of adsorbing many large molecules and has for a long time been known for its ability to remove toxic substances from the blood in accidental poisoning or overdose.
[31] Artificial cell hemoperfusion has been proposed as a less costly and more efficient detoxifying option than hemodialysis,[3] in which blood filtering takes place only through size separation by a physical membrane.
In hemoperfusion, thousands of adsorbent artificial cells are retained inside a small container through the use of two screens on either end through which patient blood perfuses.
The device consists of a cylindrical chamber imbedded with isolated hepatocytes through which patient plasma is circulated extra-corporeally in a type of hemoperfusion.
Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the gastrointestinal system.
[4] In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes.
[3] A biological red blood cell membrane including lipids and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and systemic clearance.
By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing circulatory system.
The European Commission sponsored the development of the Programmable Artificial Cell Evolution (PACE) program[78] from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions"[78] for the eventual integration into information systems.
The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill).
The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry.
The key idea was to use a massively parallel array of electrodes coupled to locally dedicated electronic circuitry, in a two-dimensional thin film, to complement emerging chemical cellular functionality.
A research proposal was successful with the European Commission and an international team of scientists partially overlapping with the PACE consortium commenced work 2008–2012 on the project Electronic Chemical Cells.
The major limitation of this approach, apart from the initial difficulties in mastering microscale electrochemistry and electrokinetics, is that the electronic system is interconnected as a rigid non-autonomous piece of macroscopic hardware.
Such cells can copy both their electronic and chemical contents and will be capable of evolution within the constraints provided by their special pre-synthesized microscopic building blocks.
[92] First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules.
