Current Affairs

RNA EDITING

TAG: GS- 3 SCIENCE AND TECHNOLOGY

CONTEXT: On October 16, 2024, Wave Life Sciences, a Massachusetts-based biotech company, pioneered clinical-level RNA editing to treat genetic disorders, providing a temporary, reversible alternative to DNA editing.

EXPLANATION:

What is RNA editing:

The term RNA editing describes molecular processes in which the information content in an RNA molecule is altered. Such changes have been observed in eukaryotes’ tRNA, rRNA and mRNA molecules but not in prokaryotes.
Demonstrating RNA editing in prokaryotes may only be a matter of time, given the range of species in which various RNA editing processes have been found.
RNA editing occurs in the nucleus and in mitochondria and plastids, which are thought to have evolved from prokaryotic-like endosymbionts.
However, most RNA editing processes are evolutionary recent developments that have arisen independently. The diversity of RNA editing mechanisms includes nucleoside modifications such as C to U and A to I, as well as non-templated nucleotide additions and insertions. RNA editing in mRNA effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence.

RNA Editing: Mechanism and Technique:

RNA Editing Process: RNA editing corrects mistakes in mRNA after synthesis but before protein formation, preventing faulty proteins associated with genetic disorders.
ADAR Enzyme: ADAR (adenosine deaminase acting on RNA) converts adenosine to inosine in mRNA, mimicking guanosine’s function and allowing for accurate protein synthesis.
Guided RNA (gRNA): A gRNA directs ADAR to specific mRNA segments, allowing site-specific RNA editing for treating genetic disorders.

Advantages and Challenges of RNA vs. DNA Editing

Advantages of RNA Editing

Challenges of RNA Editing

Temporary Changes: RNA edits are temporary, allowing effects to fade over time, which helps reduce long-term risks.
Lower Immune Reaction Risk: Uses ADAR enzymes naturally in humans, minimising immune responses.
Disease-Specific Applications: Many diseases are caused by the abnormal expression of proteins, and RNA editing can correct specific RNA transcripts related to these diseases.
Reversible Therapy: RNA editing enables therapy discontinuation if issues arise, enhancing patient safety.
Quick Response: RNA editing can quickly regulate gene expression since it works on the immediate templates for protein synthesis, allowing for faster therapeutic action.

Limited Scope: RNA editing is generally limited to altering single nucleotides or small segments, restricting the types of changes that can be made.
Specificity Issues: ADAR enzymes can affect non-targeted areas, risking side effects.
Short Duration: RNA modifications are not long-lasting, which may require repeated interventions to maintain therapeutic effects.
Repeated Treatments Needed: Effects are temporary, requiring ongoing administration.
Delivery Constraints: Lipid nanoparticles and vectors limit transport capacity for large molecules.
Immune Response: RNA editing machinery introduced into the body can trigger an immune response, potentially leading to inflammation or rejection.