Genome Editing for the Treatment of Neurofibromatosis Type I

Therapies currently in development for NF1 do not address the fundamental underlying genetic mutation that causes this disorder. In contrast, gene editing technologies, including those based on the CRISPR-Cas9 system, have the potential to correct genetic mutations and halt the progress of genetic disease. However, many of the existing gene editing and gene therapy strategies cannot be adapted to the treatment of NF1 due to the large size of the NF1 gene and diversity of mutations linked to this disease. To overcome these challenges and realize the full potential of CRISPR gene editing technologies to treat genetic disorders, we aim to develop a CRISPR-based system to correct pathogenic mutations in ~90% of the NF1 patient population by inserting a full, normal sequence into the mutated NF1 gene to restore the correct NF1 sequence. We predict that restoring the correct NF1 sequence will reverse the molecular consequences of the NF1 mutations and possibly prevent further growth or reduce the size of existing tumors.