RNA Editing: A Safer Alternative to DNA Editing with Promising Therapeutic Applications
- November 7, 2024
- Posted by: OptimizeIAS Team
- Category: DPN Topics
RNA Editing: A Safer Alternative to DNA Editing with Promising Therapeutic Applications
Sub : Sci
Sec: Biotech
Why in News
RNA editing recently gained significant attention after Wave Life Sciences, a U.S.-based biotechnology firm, became the first company to successfully treat a genetic condition through RNA editing in clinical trials. This achievement marks a milestone in precision medicine, showcasing RNA editing as a safer, reversible alternative to DNA editing.
What is RNA Editing?
Cells generate messenger RNA (mRNA) based on DNA instructions. This mRNA is used to produce proteins, and transcription errors in mRNA can lead to dysfunctional proteins, often causing genetic disorders.
RNA Editing Process: RNA editing allows correction of these errors post-mRNA synthesis but before protein production. A common technique uses adenosine deaminase acting on RNA (ADAR) enzymes to alter specific adenosine molecules in mRNA into inosine, which functions similarly to guanosine.
Guide RNA (gRNA): Directs ADAR enzymes to target mRNA sites to correct single-point mutations, restoring protein function.
ADAR (Adenosine Deaminase Acting on RNA):
Enzyme that converts adenosine (A) to inosine (I) in RNA, which is then interpreted by the cell as guanosine (G).
Enables correction of RNA sequences, allowing potential treatment for genetic disorders without altering DNA.
Reduces risks associated with permanent DNA changes and minimizes immune reactions since ADAR enzymes are naturally found in human cells.
Used in RNA editing therapies for conditions like AATD, Huntington’s disease, and neurological disorders.
Inosine: A nucleoside that mimics guanosine in RNA, enabling correction of genetic errors through RNA editing.
Guanosine: A nucleoside in RNA and DNA that pairs with cytosine, essential for genetic stability and cellular energy.
The Difference Between RNA and DNA Editing:
| DNA Editing: Alters the genome permanently, which may lead to irreversible errors and higher risk factors. Tools like CRISPR-Cas9 require bacterial proteins that could trigger immune responses. | RNA Editing: Introduces temporary changes that fade over time, allowing for risk mitigation if adverse effects arise. RNA editing relies on enzymes naturally present in humans, reducing immune system reactions. |
Advances in RNA Editing: Wave Life Sciences’ Breakthrough Therapy
The company’s WVE-006 therapy targets α-1 antitrypsin deficiency (AATD), a genetic disorder impacting the liver and lungs.
The therapy utilizes a guide RNA to direct ADAR enzymes to specific single-point mutations in the SERPINA1 gene, responsible for producing α-1 antitrypsin. Once corrected, cells can produce α-1 antitrypsin at normal levels, reducing AATD symptoms.
Exon Targeting: RNA editing also extends to exon modification, where exons code for proteins, enabling more precise therapeutic targeting. Ascidian Therapeutics is pioneering this approach to address ABCA4 retinopathy, a retinal disease.
What is RNA?
RNA (Ribonucleic Acid) is a single-stranded molecule composed of ribose sugar, phosphate groups, and nucleotide bases (adenine, guanine, cytosine, uracil).
It plays a crucial role in various biological processes, mainly in coding, decoding, regulation, and expression of genes.
Types of RNA:
Messenger RNA (mRNA): Carries genetic information from DNA to the ribosome, where proteins are synthesized.
Transfer RNA (tRNA): Helps in translating mRNA into proteins by bringing amino acids to the ribosome during protein synthesis.
Ribosomal RNA (rRNA): A structural component of ribosomes, essential for protein synthesis.
MicroRNA (miRNA): Regulates gene expression by binding to mRNA, either degrading it or inhibiting its translation into protein.
RNA plays a central role in the process of transcription (copying genetic code from DNA to RNA) and translation (using mRNA to build proteins).
About Exons and Introns:
They are parts of a gene within DNA and RNA that play distinct roles in the process of creating proteins.
Exons: Exons are segments of a gene that contain coding sequences for proteins. After a gene is transcribed into pre-mRNA, exons are spliced together to form mature mRNA. This mRNA sequence directly translates into a protein.
Exons carry the essential information needed to build proteins, which perform various functions in the body.
Introns: Introns are non-coding sections of a gene. Introns are transcribed into pre-mRNA along with exons, but are removed during RNA splicing. They do not contribute to the protein sequence and are discarded.
Although they do not code for proteins, introns play a role in gene regulation, splicing, and potentially contribute to evolution by allowing genetic recombination and mutation without affecting protein-coding sequences.