Source: HINDU

Disclaimer: Copyright infringement not intended.

Context

A biotechnology company from Massachusetts, U.S., called Wave Life Sciences, became the first company to treat a genetic disease by editing RNA at the clinical level.

This achievement is a major step forward in medicine, but scientists had predicted that RNA editing would play a big role in genetic treatments.

Read about RNA: https://www.iasgyan.in/daily-current-affairs/niab-using-next-generation-sequencing

Importance of RNA in Genetic Science

RNA is crucial for various functions in our body. One of these functions, called RNA interference, allows small RNA molecules to prevent a gene from being expressed. This function has helped make gene-editing tools like CRISPR-Cas9 effective.

The quick development of mRNA vaccines for COVID-19 also showed how important RNA is beyond just gene expression.

Read about mRNA vaccines: https://www.iasgyan.in/daily-current-affairs/mrna-vaccines

Now, with advances in medicine, RNA editing is becoming a new focus for treating specific diseases.

What is RNA Editing?

RNA editing is a process where scientists correct mistakes in the RNA. Here’s how it works:

1. Making Proteins:Cells use instructions in DNA to create messenger RNA (mRNA). Then, they use this mRNA to make proteins that the body needs.
2. Mistakes in mRNA:Sometimes, the cell makes errors in the mRNA, leading to faulty proteins. These incorrect proteins can cause serious health issues.
3. How RNA Editing Helps:RNA editing allows scientists to fix these mistakes in the mRNA before the cell makes the proteins, helping produce normal proteins instead.

How RNA Editing Works

A technique used in RNA editing involves enzymes called ADAR (Adenosine Deaminase Acting on RNA):

1. Role of ADAR:ADAR converts a molecule in RNA called adenosine into another molecule, inosine, which behaves like a different RNA building block called guanosine.
2. Correction Process:With this change, the cell spots the "mistake" and corrects it, which helps the mRNA function properly and allows the cell to make normal proteins.
3. Guided Editing:Scientists guide ADAR to specific parts of the mRNA using a helper RNA called guide RNA (gRNA), aiming to treat certain genetic disorders.

RNA Editing in Treating Diseases

Wave Life Sciences has used RNA editing to treat α-1 antitrypsin deficiency (AATD), an inherited disorder that affects the liver and lungs:

• Current Treatment:Patients with lung issues from AATD currently undergo weekly therapy, and those with liver problems need liver transplants.
• RNA Editing Solution:Wave Life Sciences used a gRNA to direct ADAR enzymes to fix specific mutations in the mRNA for the SERPINA1 gene, allowing the cell to produce the α-1 antitrypsin protein at normal levels.

Researchers are also looking at RNA editing for treating genetic eye disorders, such as ABCA4 retinopathy, and liver cancer.

Advantages of RNA Editing Over DNA Editing

RNA editing has some benefits compared to DNA editing:

1. Temporary Changes:RNA editing only makes temporary changes, so if a problem arises, doctors can stop the treatment.
2. Lower Risk of Immune Reactions:Unlike DNA editing, which uses foreign proteins, RNA editing uses ADAR enzymes already present in the human body, which reduces the risk of allergic reactions.
   

Feature	RNA Editing	DNA Editing
Type of Change	Temporary changes to RNA	Permanent changes to DNA
Effect on Genome	No change to the genome itself	Alters the genome permanently
Risk of Side Effects	Lower risk; uses enzymes already in the body	Higher risk; uses proteins from bacteria that may cause immune reactions
Reversibility	Effects fade over time; can stop treatment	Irreversible once edited
Ideal Use	Short-term treatments or reversible effects	Permanent fixes for genetic issues
Safety	Generally safer due to temporary changes	Higher risks with permanent changes
Tools Used	ADAR enzymes (already found in the body)	CRISPR-Cas9 and other tools (from bacteria)
Challenges	Needs repeated treatments; can target the wrong spot	Can cause unintended changes in DNA
Examples of Use	Treating lung and liver disorders, eye conditions	Curing genetic diseases, like sickle cell anemia

Challenges in RNA Editing

There are still some challenges with RNA editing:

1. Specificity Issues:ADAR might make unintended changes to non-targeted RNA, which could cause side effects. Scientists are working on improving guide RNA to prevent this.
2. Temporary Effects:RNA editing requires repeated treatments to maintain the effects.
3. Delivery Limitations:The current methods to deliver the ADAR-gRNA complex, such as lipid nanoparticles, can’t carry large molecules, limiting some applications.

Conclusion

RNA editing is a young field, but it has attracted attention from large pharmaceutical companies like Eli Lilly and Roche. With ongoing research and trials, RNA editing may soon become an essential tool for treating genetic diseases.

Sources:

HINDU

PRACTICE QUESTION Q.Discuss the potential of RNA editing as a tool in precision medicine and its advantages over DNA editing for treating genetic disorders. (150 Words)