Spinal-Muscular Atrophy gene therapy: From ASOs to CRISPR/Cas9

Abstract: Spinal-Muscular Atrophy (SMA) is one of the most lethal autosomal recessive diseases in whitepopulations. Mutations in SMN1 gene, most of which occur on exons No. 7 and 8, causes the disease andeventually the degeneration of neurons located in anterior horn of the spinal cord. Absence of neuronal impulseleads to generalized severe skeletal muscle atrophy.Different therapeutic strategies have been proposed for this disease some of which are in pre-clinical and someothers in clinical phase. In the present review, available and developing genetic therapeutic strategies are listed.Most of them are focused on mechanisms such as splicing alterations or gene replacement etc. There are alsosome other treatments concentrated on stabilizing SMN2 proteins and preventing neurons from degeneration.In addition to reviewing existing procedures, we will also have a look into a proposed procedure such as geneediting. In case of SMN2 gene edition and turning it into SMN1 using emerging technologies such asCRISPR/Cas9, permanent cure for the disease may be available.

Keywords:

CRISPR-Cas , Gene Editing , Spinal Muscular Atrophy , Antisense Oligonucleotides , SMN1 protein , SMN2 protein