Antisense oligonucleotide and RNA therapies in organoids for cystic fibrosis and cystinosis

About this project

The aim of this PhD project is initially to optimize AON and RNA approaches to correct splicing mutations in CFTR (or other amenable rare variants), using minigene reporter models expressed in human bronchial epithelial cell lines.

Models of the most common correctable splicing (or other) CFTR variants will then be developed in organoids to further optimize the assays with the aim of producing protocols for their delivery in the context of personalized medicine testing.

Delivery methods for these AON/RNA therapy approaches will also be investigated, namely, by comparing viral vector and mRNA approaches in organoids and introducing the use of de-immunized mRNA and proprietary LNPs in complementary models for CF during secondments at KULeuven and Mercurna. In line, potential of AON approaches will be evaluated in models for cystinosis.

The result should be a generalized approach to the application of optimized AON and mRNA therapy correctors to rare mutations causing CF and Cystinosis.

Candidate requirements and skills

Masters degree in Biochemistry, Biology, Molecular Biology, Biomedical Sciences (or similar). At least level C and good communication skills in English. Knowledge of genetics, cell culture, and PCR would be seen as a positive.