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Precision Docking of Very Large DNA Cargos in Mammalian Genomes

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.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/biological sciences/genetics and heredity/dna

Call for proposal

ERC-2018-ADG
See other projects for this call

Funding Scheme

ERC-ADG - Advanced Grant

Host institution

UNIVERSITY OF BRISTOL
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 498 578

Beneficiaries (1)

UNIVERSITY OF BRISTOL
United Kingdom
EU contribution
€ 2 498 578
Address
Beacon House Queens Road
BS8 1QU Bristol
Activity type
Higher or Secondary Education Establishments