Repair of Mutated <i>NF1</i> mRNA with Trans-Splicing Group I Intron Ribozymes.

ABSTRACT:

Background/objectives

Therapeutic strategies for Neurofibromatosis Type I (NF1) that correct the underlying pathogenic NF1 variant hold promise for restoring neurofibromin function, reducing tumor burden, and improving patient outcomes by addressing the root cause of the disease rather than its symptoms. Beyond gene editing, transcript reprogramming via RNA trans-splicing has gained attention, particularly with the recent FDA approval of two trans-splicing-based drugs for IND phase 1/2a trials. This study tests whether trans-splicing group I intron ribozymes from Tetrahymena thermophila can be used to repair pathogenic variants of NF1 (pre-)mRNA by 3'-tail replacement.

Methods

Splice sites on the NF1 mRNA were identified computationally and valida

SUBMITTER: Leier A 

PROVIDER: S-EPMC12427287 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature