CRISPR-Cas9 Guided RNA Based Model for the Silencing of Spinal Bulbar
Muscular Atrophy: A Functional Genetic Disorder
Abstract
Spinal bulbar muscular atrophy (SBMA) is a neurodegenerative genetic
disorder, which results because of a mutation in the start codon of the
Androgen Receptor (AR) gene. The mutant Androgen Receptor gene features
the polyglutamine expansion (CAG) repeats, undergoing inappropriate
post-translational modifications, which leads to development of toxin
production functionality. In order to inhibit the production of mutant
AR gene, CRISPR-Cas9 based model to cure the trinucleotide repeat
disorder is proposed in this research. CRISPR cas9 constructed guided
RNAs are expected to showed max treatment accuracy an effective
silencing method in the functional genetic disorder of SBMA. It
demonstrates the on-target and off-target scores that hold GC content
within 40 - 60%. Further validation comes from the minimum free energy
that is correlated with the gRNA’s structural accuracy. Although,
currently, there is no effective and complete cure of SBMA is available
except symptomatic treatments, CRISPR-Cas9 provides a better approach to
target this disease at the molecular level, which gives a hope to
develop an effective treatment against this currently non-curable
disease. Possible results are constructed using in-silico and
computational therapeutic approach for SBMA. The CRISPR-Cas9 protein
shows promising results in an artificial environment. Thus, this study
presents for the first time a specific possible future candidate in the
treatment of SBMA that holds potential as a therapeutic approach for a
genetic disorder. Imbued by the CRISPR mechanism and the suitability of
gRNA, this strategy can be utilized as a novel therapeutic approach.