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A DNA NANOtechology toolkit for artificial CELL design

Periodic Reporting for period 1 - NANOCELL (A DNA NANOtechology toolkit for artificial CELL design)

Reporting period: 2020-01-01 to 2021-06-30

The astonishingly rich phenomena that we observe in biology emerge from the complex behaviours and functionalities sustained by biological cells. The ability to replicate these responses in completely artificial microrobots, dubbed "artificial cells" is one of the great scientific challenges of our times that, once achieved, could revolutionise our understanding of life, its origin, and importantly have a massive impact on healthcare technologies. For instance, one could think of utilising artificial cells as in-vivo therapeutic agents, capable of sensing the presence of a disease and responding by locally producing and delivering a therapeutic agent, hence enabling personalised therapeutic solutions with reduced toxicity and lower risks compared to approaches based on biological cells.

Artificial cells, are typically constructed from the bottom-up, starting from non-living molecular components that make up their structural elements (e.g. artificial membranes) and give them the ability to respond to stimuli. Most often scientists constructing artificial cells borrow molecular components from biological ones, using them for the same purpose for which they had evolved in the first place. While very powerful, this approach is somewhat limited, as nothing forbids us from including non-biological and non-natural components in artificial cells, which can further expand their range of capabilities and afford overall better control on their responses.

NANOCELL aims to construct artificial cells almost entirely reliant on non-biological, synthetic DNA nanostructures, utilising the tools developed in the now well-established research field of DNA nanotechnology. This approach sees DNA as a building material, rather than a genetic element, and exploits the selectivity of base-pairing to construct nanoscale objects of very well-defined structure and interactions. In our artificial cells, synthetic DNA nanostructures fulfill both structural and functional roles, roughly equivalent to what proteins do in biological cells.
A central element of the NANOCELL platform are membrane-less organelles self-assembled from DNA nanostructures. These will enable to segregation of responsive elements in different environments within each artificial cells, a key pre-requisite for building complex responses.
The first year of NANOCELL has been seriously impacted by COVID as we have experienced extended periods of laboratory closure and restricted access for most of the year. Nonetheless, we have managed to make good progress, particularly on the structural aspects of the DNA-based artificial cells. The team has deepened our understanding of the DNA-based building blocks which are central to NANOCELL, and developed protocols to construct complex cell-like architectures in which DNA-based organelles are enclosed in a semi-permeable lipid-DNA membranes, similar to the one attached. We are now working on optimising these protocols to improve their robustness and throughput, while in parallel working on new functionalities for the artificial organelles, which will in turn enable us to engineer complex behaviours in the artificial cells. These include the ability to respond to a large number of environmental stimuli, that of capturing and releasing molecular cargoes, and of triggering the self-assembly of other types of nano-structures which will play a functional role in the constructed artificial cells.
By the end of the project, NANOCELL will have developed a comprehensive, DNA-nanotechnology-based toolkit for the construction of artificial cells.
This toolkit will enable one to prescribe complex behaviours such as environmental sensing, communication with biological and artificial cells, information processing, synthesis/capture/release of functional molecular cargoes. Importantly this range of responses will be controllable via the modular combination of DNA-based organelles, each designed to perform specific tasks and interacting with other organelles to produce complex emergent functionalities.
A DNA-based artificial cell. The cyan objects are synthetic organelles made of DNA nanostrucures.