Prelims: Current events of national and international importance | Science & Technology
Why in News?
Recently, a study published in Nature reported a new genome-editing strategy (PERT) that can potentially treat multiple genetic disorders caused by nonsense mutations.
- Genes – They are made of DNA (deoxyribonucleic acid).
- It contains instructions for cell functioning and the characteristics that make a person unique.
Genetic disorders occur when a mutation (a harmful change to a gene, also known as a pathogenic variant) affects an individual’s genes. It disrupts the cell’s ability to build a complete, functional protein.
- Genome editing – Technologies that give scientists the ability to change an organism's DNA.
- It allows genetic material to be added, removed, or altered at particular locations in the genome.
- It is also called gene editing. And the best example is CRISPR-Cas9.
- Background – A nonsense mutation is a type of genetic mutation where a wrong DNA letter changes a normal codon into a “stop” codon.
- A codon is a group of 3 DNA/RNA letters that tells the cell which amino acid to add to a protein.
- Nonsense mutations account for about one-fourth of all known disease-causing genetic changes.
- As it stops protein synthesis early.
- Mutation-Specific Therapy – Currently, each mutation requires a separate therapy, making treatment slow and costly.
Genome editing does not involve the introduction of foreign genetic material while genetic engineering does.
- New Technique – PERT (Prime-Editing-mediated Readthrough of premature Termination codons).
- This technique uses a normal tRNA (transfer RNA) to create a suppressor tRNA permanently.
- The suppressor tRNA bypasses early stop signals so a full protein is made.
- Hence, the PERT technique becomes applicable to many rare genetic diseases.
Protein synthesis happens when information passes from DNA to mRNA to tRNA and then to the ribosome.
- Mechanism – Human cells contain 418 tRNA genes. Leucine, arginine, tyrosine, and serine tRNAs are identified as promising candidates among them.
- Prime Editing – tRNA genes are hard to edit, so scientists used a special gene-editing method called prime editing with many guide RNAs to find the right spot.
- They also developed a new editing enzyme called PE6c, which made the process more accurate and effective.
- Key Results – Editing efficiency – 60–80% that is higher than the standard repair method at 10–20%.
- Restored enzyme activity in Batten disease, Tay-Sachs disease, etc. (17–70% of normal).
- No major off-target effects or toxicity observed.
- Challenges – Issues in delivery to different tissues, long-term safety, and durability.
- Clinical translation still requires further validation.
- Significance – Offers a single universal therapeutic platform for precision gene therapy with broad clinical applications in rare genetic disorders.
Quick Fact
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CRISPR-Cas9
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- CRISPR – It stands for Clustered Regularly Interspaced Short Palindromic Repeats.
- CRISPR-Cas9 – Most prominent technology that enables editing parts of the genome by removing, adding or altering sections of the DNA sequence.
- Components – Consists of two key molecules that introduce a change mutation into the DNA.
- Cas9 – An enzyme that acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome.
- Guide RNA (gRNA) – The gRNA is designed to find and bind to a specific sequence in the DNA.
- Mechanism –
- The Cas9 follows the guide RNA to the same location in the DNA sequence and makes a cut across both strands of the DNA.
- At this stage, the cell recognises that the DNA is damaged and tries to repair it.
- Can be used to introduce changes to one or more genes in the genome of a cell of interest.
- The technology replicates a natural defence mechanism in some bacteria that uses a similar method to protect itself from virus attacks.
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Reference
TH | Single Genome-Editing Strategy for Multiple Genetic Disorders
