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Expanded genetic alphabets for orthogonal encoding of genetic information

Project description

Is it possible to rewrite life’s alphabet?

If DNA is nature’s code, would it be possible to rewrite it with new letters? The ERC-funded OrthoScript project is developing a breakthrough platform to synthesise, replicate, and evolve DNA and RNA using alternative genetic alphabets. By engineering bespoke polymerase enzymes, the team aims to create high-fidelity systems that go beyond nature’s four-letter code, increasing information density and unlocking entirely new forms of molecular data storage. These tools could also enable orthogonal genetic systems, paving the way for revolutionary advances in synthetic biology, evolvability studies, and biotech applications. OrthoScript reimagines the building blocks of life and what they could be used for.

Objective

In OrthoScript, we aim to build a technology platform for the efficient synthesis, replication and evolution of DNA and RNA comprising alternative genetic alphabets that are either orthogonal to the natural alphabet or expand its combinatorial potential and information density. Our approach involves the leveraging of protein design and evolution approaches to generate bespoke DNA and RNA polymerase enzymes for the encoded synthesis and sequencing of expanded genetic alphabets with high efficiency and fidelity. If successful our approach unlocks the potential of these new alphabets for information storage and enables a systematic investigation of the relationship between complexity (informational density), evolvability and phenotypic diversity in informational biopolymers. The same polymerases are critical for the scalable integration of an expanded alphabet into an orthogonal replisome in a living cell. If realised, we provide a technology platform for the encoding of information in expanded, orthogonal genetic alphabets both in vitro and in bacteria with transformative potential in applications like molecular information storage and genetic code expansion.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-ADG

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Host institution

UNITED KINGDOM RESEARCH AND INNOVATION
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 497 496,00
Address
POLARIS HOUSE NORTH STAR AVENUE
SN2 1FL SWINDON
United Kingdom

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Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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