Question

The “reading frame hypothesis” can explain the difference in
phenotype between Duchenne and Becker muscular dystrophies (DMD
and BMD respectively), diseases which are both caused by mutations
affecting the gene encoding the protein dystrophin. How has our
understanding of the molecular bases of these two diseases led to
development of molecular therapies for DMD using antisense
oligonucleotides to modulate dystrophin RNA splicing, and involving a
mechanism of so-called exon skipping? (min 500words)

Answer 1

the mechanism of exon skipping occurs when there are non sense or missense mutations taking place in the BRCA1 genes or other genes. In this process, there will be skipping of Exxon’s, which may be one or more, and this process takes place in the nucleus. This is also referred to as NAS or nonsense mediated altered splicing.

In the genetic therapies or approaches, mostly, there would be an attempt to compensating the loss of a gene function as there would be a recombinant cDNA introduced in the tissues or meninges. In order to cure the Duchenne and Becker muscular dystrophy exon splicing and antisense oligonucleotide mechanisms have been used.

The molecular basis of the two different types of diseases. These two are referred to as D/BMD. The reading frame hypothesis in both the diseases differ from almost 30% or greater. In the method described for treating these two devices, there have been attempts at correction of gene mutations taking place at the post transcriptional level. According to this strategy, there will be modifications in the component binding of splicesomes, where, there would be antisense hybridisations which is of a high affinity. There is biostsbility in the splicomers , which are designed to be stable such that there would be restoration of reading frames after mutation skipping. In the DND, ere is causation of mutations in the dystrophin gene , for the bmd, there would be Rane shift deletion of central gene portion of almost 50%.

BMD is the milder form, which may be asymtomatic for most people, whereas in dmd, the dystrophin gene deficiency takes place in striated muscles. Here MDx muscle cells with the spliceomers end to generation of an in frame dystrophin transcript and restoration of expression of dystrophin.