In News:

Wave Life Sciences became the first biotechnology company to treat a genetic condition by editing RNA at the clinical level.

• What is RNA Editing?

• Definition: RNA editing is the modification of messenger RNA (mRNA) after it’s synthesized from DNA but before it is translated into proteins.
• Process: mRNA consists of exons (coding regions) and introns (non-coding regions). Exons code for proteins, while introns are removed before protein synthesis.

• Types of RNA Modifications:

• Addition: Insertion of a nucleotide.
• Deletion: Removal of a nucleotide.
• Substitution: Replacement of one nucleotide with another.

• Mechanism of RNA Editing:

• Involves Adenosine Deaminase Acting on RNA (ADAR) enzymes.
• ADAR enzymes modify adenosine to inosine, which is recognized as guanosine, allowing mRNA to be corrected.
• Guide RNA (gRNA) directs ADAR enzymes to the specific mRNA region for editing.

• Clinical Use of RNA Editing:

• Wave Life Sciences used RNA editing to treat α-1 antitrypsin deficiency (AATD), a genetic disorder.
• Other potential applications include treating diseases such as Huntington’s disease, Duchenne muscular dystrophy, Parkinson’s disease, obesity, and neurological disorders.

• Challenges in RNA Editing:

• Temporary Effects: RNA editing provides temporary changes, requiring repeated treatments for sustained effects.
• Delivery Issues: Current delivery methods, like lipid nanoparticles and adeno-associated virus vectors, have limitations in carrying large molecules.
• Specificity: ADARs may cause unintended changes in non-target regions of mRNA, leading to potential side effects.

• Comparison: RNA Editing vs. DNA Editing:

• Safety: RNA editing causes temporary changes and presents fewer risks than DNA editing, which makes permanent alterations to the genome.
• Immune Response: RNA editing uses enzymes naturally found in the body (ADAR), which reduces the risk of immune reactions, unlike DNA editing tools like CRISPR-Cas9 that can trigger immune responses.

• Significance of RNA:

• Structure: RNA is a nucleic acid, similar to DNA but typically single-stranded. It consists of a backbone of ribose sugars and phosphate groups, with bases adenine (A), uracil (U), cytosine (C), and guanine (G).
• Types of RNA:

• Messenger RNA (mRNA): Carries genetic information from DNA to ribosomes for protein synthesis.
• Ribosomal RNA (rRNA): Forms the core of the ribosome and catalyzes protein synthesis.
• Transfer RNA (tRNA): Transfers amino acids to ribosomes during protein synthesis.
• Regulatory RNAs: Regulate gene expression.

• α-1 Antitrypsin Deficiency (AATD):

• A genetic disorder where the protein α-1 antitrypsin accumulates in the liver, damaging both the liver and lungs.
• Treatments include weekly intravenous therapy or, in severe cases, liver transplants.
• RNA editing offers a potential new treatment approach.

• Global Impact:

• RNA editing is still in its early stages but shows promise for treating a wide range of genetic and chronic conditions.
• Ongoing research and clinical trials suggest RNA editing could become a key part of future gene-editing therapies.