Context:

Recently, a biotechnology company in the USA named Wave Life Sciences became the first company to treat a genetic condition in humans by editing RNA at the clinical level. 

What is RNA Editing?

• Cells use DNA instructions to synthesize mRNA, which is then read to produce proteins. During this process, errors in mRNA can lead to faulty proteins, causing various disorders. 
• RNA editing allows scientists to fix mistakes in the mRNA after the cell has synthesised it but before the cell reads it to make the proteins.

Working of RNA Editing: 

• One such technique involves a group of enzymes called adenosine deaminase acting on RNA (ADAR).
• ADAR enzymes convert some of the adenosine blocks in mRNA to inosine, which acts like guanosine. 
• This change helps the cell recognize and fix a problem in the mRNA, allowing the cell to produce normal proteins. 
• Scientists use gRNA to direct ADAR to precise locations in the RNA sequence, ensuring targeted modification.

RNA v. DNA Editing

Safety and flexibility: DNA editing makes permanent changes to a person’s genome and sometimes this can lead to irreversible errors. On the other hand, RNA editing makes temporary changes, allowing the effects of the edits to fade over time.

Reduced Immunogenicity: DNA editing tools like CRISPR-Cas9 use bacterial proteins that can trigger immune reactions, while RNA editing relies on naturally occurring ADAR enzymes, lowering allergy risk.

• This makes RNA editing safer for patients needing repeated treatments or with immune sensitivities.

Precision in Treating Single-Point Mutations: RNA editing is particularly suitable for correcting single-point mutations without altering the genome, making it ideal for various inherited disorders.

Challenges in RNA editing

Specificity Issues: ADARs can perform adenosine-inosine changes in both targeted and non-targeted parts of mRNA, or skip the targeted parts altogether. 

• When ADARs don’t align with the adenosine of interest, potentially serious side-effects could arise.

Transience of RNA Editing: Temporary edits necessitate repeated treatments to maintain therapeutic benefits, increasing treatment complexity. 

Delivery Limitations: Current methods to deliver the gRNA-ADAR complex, such as lipid nanoparticles and adeno-associated viruses (AAV), face limitations in terms of carrying large molecules, thus restricting RNA editing’s scope.

Way Ahead

• RNA editing offers a new paradigm in molecular medicine, addressing where DNA editing falls short in terms of flexibility and safety. 
• Although RNA editing is in its nascent stage, there are already at least 11 biotechnology companies worldwide developing RNA editing methods for a range of diseases. 
• As research and clinical trials advance in the field of RNA editing, it seems like only a matter of time before RNA editing becomes a fixture of the gene-editing toolkit in clinical practice.