What is Exon Skipping?
Exon skipping is a genetic therapy technique that aims to treat certain genetic disorders by "skipping" over faulty sections of DNA, known as exons, during the process of gene expression. This allows the production of a partially functional protein instead of a completely non-functional one, thereby reducing the severity of the disease.
How Does Exon Skipping Work?
The process involves the use of synthetic molecules called antisense oligonucleotides (AONs). These AONs bind to specific sequences of RNA, masking the faulty exon so that it is skipped during mRNA splicing. As a result, the remaining exons are joined together, producing a shorter but functional protein.
Which Pediatric Conditions Can Be Treated with Exon Skipping?
One of the most notable applications of exon skipping is in the treatment of Duchenne Muscular Dystrophy (DMD), a severe muscle-wasting disease. DMD is caused by mutations in the dystrophin gene, and exon skipping can help restore the production of a truncated, yet functional, dystrophin protein. Other potential applications include certain types of spinal muscular atrophy (SMA) and cystic fibrosis.
Reduced Severity: By allowing the production of a partially functional protein, the severity of the genetic disorder can be significantly reduced.
Targeted Therapy: This technique is highly specific, targeting only the faulty exon and minimizing off-target effects.
Potential for Early Intervention: Since many genetic disorders manifest early in life, exon skipping can be used for early intervention, potentially improving long-term outcomes.
Delivery Methods: Efficiently delivering AONs to the target tissues, especially in systemic conditions like DMD, remains a significant hurdle.
Long-term Efficacy: As of now, the long-term efficacy and safety of exon skipping treatments are still being studied. Regular monitoring and repeated treatments may be required.
Personalization: The technique often needs to be tailored to the specific mutation in each patient, complicating its widespread application.
What Are the Current Exon Skipping Therapies Available?
Several exon skipping therapies have received regulatory approval. For instance, eteplirsen (marketed as Exondys 51) has been approved for the treatment of DMD. These therapies are designed for specific exon mutations, such as exon 51 skipping in the case of eteplirsen.
What is the Future of Exon Skipping in Pediatrics?
The future of exon skipping in pediatrics looks promising with ongoing research aimed at overcoming current limitations. Advances in delivery methods, such as nanoparticles and viral vectors, may improve the efficiency of AON delivery. Additionally, CRISPR/Cas9 technology is being explored to enhance the precision and efficacy of exon skipping.
Conclusion
Exon skipping represents a revolutionary approach in the field of pediatric genetic therapy, offering hope for conditions like Duchenne Muscular Dystrophy and other genetic disorders. While challenges remain, ongoing research and technological advancements hold the potential to make exon skipping a mainstay in pediatric treatment regimens.
