Single Genome-editing Strategy Can Help Treat Multiple Disorders

Syllabus: GS3/Science and Technology

Context

• A study in Nature recently revealed that researchers have developed a method to address many nonsense mutation diseases using a single genome-editing strategy.

About

• Their approach is called Prime-Editing-mediated Readthrough of premature termination codons (PERT).
• It reprogrammes one of the cell’s own genes into a tool to override premature stop signals, allowing the cell to ignore the faulty instruction and complete the protein.
• The study offers a proof-of-concept for a gene-agnostic therapy that could benefit many rare diseases caused by nonsense mutations.

Genetic Disorders and Nonsense Mutations

• Genetic disorders often stem from small errors in the DNA sequence with major consequences.
  • Many diseases like cystic fibrosis and Batten disease can be traced to changes disrupting the cell’s ability to build a complete, functional protein. 
• Nonsense Mutation: One particularly common reason is the nonsense mutation, where a single incorrect DNA letter inserts a premature stop signal.
  • When the cell encounters it, protein production ends too early, leaving the body without important enzymes, transporters or structural components.
  • Nonsense mutations account for about a quarter of all known disease-causing genetic changes. 
• Therapy: Each one halts a different protein at a different point, creating a wide range of disorders that, at present, require separate treatments.
  • Each therapy needs to be designed, tested and approved on its own. This is a slow and expensive process.

Genome

• The genome is the entire set of DNA instructions found in a cell. 
• In humans, the genome consists of 23 pairs of chromosomes located in the cell’s nucleus, as well as a small chromosome in the cell’s mitochondria.
• A genome containsall the information needed for an individual to develop and function.

Gene Editing

• Genome editing technologies enable scientists to make changes to DNA, leading to changes in physical traits, like eye color, and disease risk.
  • These technologies act like scissors, cutting the DNA at a specific spot. Then scientists can remove, add, or replace the DNA where it was cut.
• The first genome editing technologies were developed in the late 1900s.
  • More recently, a new genome editing tool called CRISPR, invented in 2009, has made it easier to edit DNA. 
  • CRISPR is simpler, faster, cheaper, and more accurate than older genome editing methods. 

Gene Therapy

• It is a technique that uses genes to treat, prevent, or cure diseases by:
  • Replacing faulty genes,
  • Deactivating harmful genes,
  • Introducing new genes to restore health.
• There are two different categories of gene therapies: germline therapy and somatic therapy.
  • Germline therapies change DNA in reproductive cells (like sperm and eggs). Changes to the DNA of reproductive cells are passed down from generation to generation. 
  • Somatic therapies, on the other hand, target non-reproductive cells, and changes made in these cells affect only the person who receives the gene therapy.

Conclusion

• While genetic technologies offer promising tools for conservation, their application must be guided by scientific rigor, ethical considerations, robust regulation, and ecological sensitivity. 
• A balanced, interdisciplinary approach is key to ensuring their responsible and effective use.

Source: TH