Innovating Works

GENESHUTTLE

Financiado
What does it take to build an artificial virus?
Using rational design with DNA origami, we propose to create synthetic virus-like assemblies capable of accomplishing cell-invading and gene expression functionalities known so far only from natural viruses. We envision these asse... Using rational design with DNA origami, we propose to create synthetic virus-like assemblies capable of accomplishing cell-invading and gene expression functionalities known so far only from natural viruses. We envision these assemblies to be useful for studying and testing viral import mechanisms, and also for gene delivery, enabling fundamental studies and potential medical applications. The objectives include selecting and invading a target cell type, systematically solving the challenges of endosomal escape and nuclear delivery, and inducing the expression of user-defined genetic information in the nucleus. To achieve these objectives, we will recreate and experimentally test mechanisms believed to be used by viruses, including receptor-mediated endocytosis, stimulus-dependent lipid membrane penetration, membrane fusion, active cytosolic transport, and nuclear import. We foresee building synthetic shells carrying genetic information stored in nucleic acids, which we refer to as the gene shuttle. The particles will optionally include a membrane envelope and user-defined surface features to mediate receptor-ligand interactions with cell membranes, and they will be capable of stimulus-dependent conformational changes to trigger membrane fusion or membrane penetration. They will shed structural elements on the path to the nucleus, similar to viruses. In addition to delivering genes for fluorescent markers, as a proof of concept demonstration we plan to use the gene shuttle to deliver the genetic information for expressing chimeric antigen receptors (CAR) in a T cell line, which promises to be of use in cancer immunotherapy. The project promises to yield a gene delivery system with capabilities beyond current synthetic vectors, which struggle to overcome the many cellular barriers to deliver and express genetic cargo. For safety reasons, the gene shuttle will by design be unable to assemble in the context of a cell to prevent uncontrolled autonomous replication. ver más
30/04/2027
TUM
2M€
Perfil tecnológico estimado
Duración del proyecto: 69 meses Fecha Inicio: 2021-07-24
Fecha Fin: 2027-04-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-07-24
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2020-ADG: ERC ADVANCED GRANT
Cerrada hace 4 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
TECHNISCHE UNIVERSITAET MUENCHEN No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5