2026-09-24T07:24:59Zhttps://api.repository.cam.ac.uk/server/oai/request

oai:www.repository.cam.ac.uk:1810/3955602026-01-28T01:43:39Zcom_1810_195217com_1810_256065col_1810_219484

Designer DNA Condensates: From Multiphase Architectures to Synthetic Exosome Release https://doi.org/10.17863/CAM.125014 Tanase, Diana 0000000296606730 Di Michele, Lorenzo In biological systems, complexity stems from the intricate organisation of molecular components. DNA nanotechnology and synthetic biology allow the construction of programmable model systems that reduce complexity in a controlled manner, enabling targeted investigation and rational design. By leveraging the programmability of nucleic acids, it is possible to construct complex architectures with precise control over structure and function. This work focuses on developing DNA-based platforms for advanced biomimetic materials and targeted cargo release, bridging insights into self-assembly with practical biotechnological solutions. The first part of this work addresses the biophysical principles underpinning the emergence of multi-phase biomolecular condensates, which are critical for cellular organisation but remain poorly understood. A synthetic model system is introduced based on DNA nanostructures capable of forming monophasic or biphasic condensates. This system allows precise control over key condensate features, including the degree of interphase mixing and the relative size and spatial arrangement of internal domains. This modular approach provides an intuitive understanding of phase behaviour, o"ering insights to address open questions on multiphase condensation in biology and aiding the design of functional biomolecular condensates in vitro, in synthetic cells, and in living cells. Building upon the control over DNA condensate phase behaviour, the subsequent part of this thesis focuses on integrating synthetic exosomes within these engineered DNA phase-separated condensates. I demonstrate the capability to programmatically localise synthetic exosomes either inside or outside the DNA condensates. Critically, I achieve their controlled release in response to stimuli specifically targeting distinct DNA phases, enabling highly localised and stimulus-responsive cargo delivery. Finally, this work demonstrates the targeted deposition of the released synthetic exosomes onto amphiphilic receiver condensates. Collectively, this work illustrates the versatility of nucleic acids as a foundational ma- terial for building responsive biomimetic systems, advancing both basic understanding and applied biomaterial design. University of Cambridge 2025-10-14 Thesis Doctoral Doctor of Philosophy (PhD) eng European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme: ERC-STG No 851667 – NANOCELL https://www.repository.cam.ac.uk/handle/1810/395560 https://www.repository.cam.ac.uk/bitstreams/1f596893-f2fc-451e-aa62-ed6f6fcb6244/download 19fde5397de3eb43f1db737a92257a0a https://www.repository.cam.ac.uk/bitstreams/b3bf5de9-e4df-42fa-bff8-316ed7a0c63b/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ Condensates DNA nanotechnology LLPS Synthetic Biology Synthetic cells