MaxFUSE LNPS
Financiado
Engineering lipid nanoparticles to target and escape the endosome, deliver their...
Engineering lipid nanoparticles to target and escape the endosome, deliver their cargo and perform better as breast cancer therapies
There is a strong need for personalised genetic medicines for the treatment of advanced breast cancer. LNP-mRNA nanomedicines have already been proven as safe and cost effective in the SARS-CoV-2 vaccines. However, cancer treatmen...
There is a strong need for personalised genetic medicines for the treatment of advanced breast cancer. LNP-mRNA nanomedicines have already been proven as safe and cost effective in the SARS-CoV-2 vaccines. However, cancer treatments often require (i) repeat dosing (ii) controlled immune response (iii) adaptability to combat drug resistance. There are several LNP-RNA clinical cancer trials ongoing, many of which have reported challenges with toxicity, performance and specificity (off target effects). For an LNP-RNA cancer therapeutic to function, they need to localise in the correct organ, enter the cancer cells and escape the cellular (endosomal) processing pathway to release their RNA cargo. In current LNP-RNA formulations only a small fraction (<10 %) of LNPs successfully escape the endosome. However, these ‘null’ LNPs can still contribute to toxicity which places huge restrictions on their clinical application and performance. The aim of this proposal is to provide mechanistic insight into the endosomal escape of LNPs and use nanoscale engineering to target the endosome and improve LNP endosomal escape. This is particularly relevant in breast cancer as the majority of LNP systems are optimised for liver applications and designed to undergo fusion under ‘healthy’ endosomal conditions. In breast cancer, the composition (lipid, protein) and environment (pH) of the endosome differ significantly between healthy and cancer cells.
Objectives:
- Use omics approaches to quantify key differences in the endosome in healthy and breast cancer sub type cells and develop breast cancer sub type endosome models
- Design LNPs with enhanced fusion to endosomes using (i) lipid composition (ii) protein – protein / lipid interactions (iii) pH mediated fusion
- Validate novel LNPs with increased endosomal fusion and lower toxicity for breast cancer treatment
ver más
Duración del proyecto: 66 meses
Fecha Inicio: 2023-11-03
Fecha Fin: 2029-05-31
Fecha Fin: 2029-05-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-11-03
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG:
ERC STARTING GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
KUNGLIGA TEKNISKA HOEGSKOLAN
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5