PhD Studentship: CRISPR-based gene therapeutic for multiple sclerosis linked to NR1H3 mutations

University of Sheffield - Neuroscience

Multiple sclerosis (MS) is a chronic immune mediated inflammatory disease of the central nervous system (CNS) and is the most common cause of non-traumatic disability in young and middle-aged adults. It affects approximately 1:1000 individuals accounting for 100,000 cases in the UK, and 2.5 million cases worldwide. It is more prevalent in Caucasians of northern European ancestry and has a peak onset at age 20 – 30 years.

MS was originally considered an autoimmune disease triggered by exposure to environmental agents; however, recent reports have clearly demonstrated the existence of a genetic component implicated in the disease. A recently published study described the identification of mutations in the nuclear receptor NR1H3 p.Arg415Gln in seven MS patients. In the current project, we will use CRISPR/Cas9 gene editing approach for targeting guide RNA molecules to correct the mutation in NR1H3 gene. Unlike previous studies using a single RNA sequence to create a double-stranded DNA break, two guide RNA hybridizing outside of the 5’ and 3’ region of the expansion will be used, in order to correct the mutation in NR1H3 in cell and animal model of MS. Similar approaches have been recently used to remove exon 23 of dystrophin gene demonstrating significant rescue of the muscular dystrophy phenotype in mice 1-3.

1 Tabebordbar, M. et al. Science 351, 407-411, (2016).
2 Nelson, C. E. et al. Science 351, 403-407, (2016).
3 Long, C. et al. Science 351, 400-403, (2016).


This scholarship covers fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.

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Northern England