Project description
Innovative technology to deliver large functional DNA circuitry into mammalian genomes
Gene editing is developing at breathtaking speed and is currently highly effective for local, small genomic DNA edits and insertions. Gene synthesis is now capable of producing thousands of DNA base pairs. The next challenge is genome engineering with the delivery of large multi-component DNA circuitry, including programmable functionalities. The EU-funded DNA-DOCK project aspires to create ground-breaking, easy-to-use technology to enable docking of large DNA cargos with base-pair precision into mammalian genomes, generating multifunctional circuits. Researchers will employ multiple sophisticated technologies to achieve these ambitious goals and accomplish precise DNA integration into specific genomic sites.
Objective
Gene editing has developed at breath-taking speed. In particular CRISPR/Cas9 provides a tool-set thousands of researchers worldwide now utilize with unprecedented ease to edit genes, catalysing a broad range of biomedical and industrial applications. Gene synthesis technologies producing thousands of base pairs of synthetic DNA have become affordable. Current gene editing technology is highly effective for local, small genomic DNA edits and insertions. To unlock the full potential of this revolution, however, our capacities to disrupt or rewrite small local elements of code must be complemented by equal capacities to efficiently insert very large synthetic DNA cargos with a wide range of functions into genomic sites. Large designer cargos would carry multicomponent DNA circuitry including programmable and fine-tuneable functionalities, representing the vital interface between gene editing which is the state-of-the-art at present, and genome engineering, which is the future. This challenge remained largely unaddressed to date.
We aspire to resolve this bottleneck by creating ground-breaking, generally applicable, easy-to-use technology to enable docking of large DNA cargos with base pair precision and unparalleled efficiency into mammalian genomes. To achieve our ambitious goals, we will apply a whole array of sophisticated tools. We will unlock a small non-human virus to rational design, creating safe, flexible and easy-to-produce, large capacity DNA delivery nanodevices with unmatched transduction capability. We will exploit a range of techniques including Darwinian in vitro selection/evolution to accomplish unprecedented precision DNA integration efficiency into genomic sites. We will use parallelized DNA assembly methods to generate multifunctional circuits, to accelerate T cell engineering, resolving unmet needs. Once we accomplish our tasks, our technology has the potential to be exceptionally rewarding to the scientific, industrial and medical communities.
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
BS8 1QU Bristol
United Kingdom