Innovating Works

Holo-GT

Financiado
Custom designed gene editing of induced epidermal stem cells for gene therapy of...
Custom designed gene editing of induced epidermal stem cells for gene therapy of genetic diseases of squamous epithelia Holo-GT will define innovative ex vivo gene therapy of dominant genetic skin disease, by using Epidermolysis Bullosa (EB) as a model system. EB is a group of dominantly or recessively inherited, devastating, incurable diseases mar... Holo-GT will define innovative ex vivo gene therapy of dominant genetic skin disease, by using Epidermolysis Bullosa (EB) as a model system. EB is a group of dominantly or recessively inherited, devastating, incurable diseases marked by structural fragility of the integuments. The applicant has shown that combined ex vivo cell and gene therapy can cure the skin of recessive LAMB3-Junctional EB. This lifesaving procedure unveiled that the human epidermis is sustained solely by long-lived stem cells, detected as holoclone-forming cells, which generate transient progenitors referred to as meroclones and paraclones. However, over 50% of EB are dominantly inherited, making gene addition unsuitable. Gene editing does not efficiently correct epidermal stem cells, which define a small proportion of clonogenic keratinocytes and cannot be prospectively isolated. Holo-GT aims at designing a safe and efficacious protocol for dominant forms of EB through: • Molecular characterization of the keratinocyte clonal types and pathways sustaining holoclone-forming cells by single-cell RNA profiling. • Generation of induced holoclone-forming cells (iHolo) by transient expression of specific sets of transcription factors (identified in aim 1) able to reprogram progenitors into holoclone-forming cells. • Development of custom-engineered CRISPR/Cas nucleases, based on selection-based directed evolution or structure-guided mutagenesis, able to fully distinguish wild type and mutant alleles. • Using this newly developed CRISPR/Cas system, gene editing of iHolo prepared from keratinocyte cultures initiated from patients with dominant forms of EB. Holo-GT could tackle not only dominant EBs but also other dominant genetic diseases of the epidermis and other squamous epithelia, as well as recessive forms of EB, particularly those characterized by the well-known depletion of stem cells, which could be rescued by the reprogramming of transient progenitors into holoclone-forming cells (iHolo). ver más
31/08/2026
UNIMORE
2M€
Duración del proyecto: 61 meses Fecha Inicio: 2021-07-05
Fecha Fin: 2026-08-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-07-05
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
UNIVERSITA DEGLI STUDI DI MODENA E REGGIO EMI... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5