Combining nonsense mutation suppression therapy with nonsense-mediated decay inhibition in neurofibromatosis type 1.

ABSTRACT: Neurofibromatosis type 1 (NF1) results from germline mutations in the tumor-suppressor gene NF1 and predisposes patients to developing nervous system tumors. Twenty percent of NF1 patients harbor nonsense mutations resulting in premature termination codons (PTCs). Nonsense suppression therapies can facilitate ribosomal readthrough of PTCs to restore full-length protein, but their potential in NF1 is underexplored. We developed a minipig model of NF1 carrying a PTC to test whether nonsense suppression could restore expression of the NF1-encoded protein neurofibromin in vitro and in vivo. Nonsense suppression did not reliably increase neurofibromin in primary NF1^-/- Schwann cells isolated from minipig neurofibromas but could reduce phospho

SUBMITTER: Osum SH 

PROVIDER: S-EPMC10384610 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature