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SCRIBE

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RNA-based gene writing in human cells

CRISPR development has enormously accelerated genetic engineering principles, and precise methods to modify small alleles (such as base or prime editing) are now available. However, generating large genomic changes still presents... ver más

30/04/2029

UPF

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAT POMPEU FABRA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 321

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-12-20

ERC-2023-COG: ERC CONSOLIDATOR GRANTS Scope:Objectives

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UPF

2.00M€ | Lider

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Duración del proyecto: 64 meses Fecha Inicio: 2023-12-20
Fecha Fin: 2029-04-30

Líder del proyecto

UNIVERSITAT POMPEU FABRA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 321

Presupuesto del proyecto 2M€

Descripción del proyecto CRISPR development has enormously accelerated genetic engineering principles, and precise methods to modify small alleles (such as base or prime editing) are now available. However, generating large genomic changes still presents enormous challenges. Large modifications, such as gene transfers, are performed generally with viral vectors, which have been associated with toxicities in the clinic, and often lack versatility needed for basic science experimentation. Newer CRISPR-based techniques for gene transfer suffer from significant efficacy and safety problems when used for large message writing. The overall goal of SCRIBE is to create new strategies for gene writing and define their molecular principles. These new writers will use RNA to both encode and transfer the message. The SCRIBE strategies will take advantage of the retrotransposon capacity for writing genes from RNA, and the precision of CRISPR in addressing specific sites of the genome. Thus, the find function will be dominated by CRISPR components, and copy-paste activity will be executed by retroelement components. To develop and optimize such a technology, we will use evolutionary analysis to select those retroelements with the highest activity and orthogonality, and modulate their message writing capacity by engineering their components. We will test various CRISPR and retrotransposon combinations, and adapt both of them to converge into a unified molecular machine. We will use artificial intelligence applied to protein design and a novel concept of synthetically oriented evolution to accelerate emergence of the new function. Finally, we will deploy new gene writing principles for RNA-based in vivo gene delivery. In sum, we will develop a new family of tools for engineering life. The real breakthrough will be the establishment of gene writing as a simple and general method for both research advancement and applied purposes.

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