One-Shot Therapy to Lower Bad Cholesterol (Health)
One-Shot Therapy to Lower Bad Cholesterol (Health)
Why In News:
Emerging gene-silencing and gene-editing therapies were in news that promise long-lasting reduction of LDL, or 'bad', cholesterol with a single or infrequent dose, marking a shift from daily pills to durable biological interventions.
Understanding LDL Cholesterol and PCSK9
LDL cholesterol, often called “bad cholesterol,” can build up inside artery walls and form plaques. This can increase the risk of heart attacks and strokes.
The liver helps control LDL levels by removing LDL particles from the blood through special proteins called LDL receptors.
PCSK9 is a protein that controls these LDL receptors. When PCSK9 attaches to an LDL receptor, the receptor is broken down, so the liver removes less LDL from the blood.
Blocking PCSK9 helps preserve more LDL receptors on liver cells. As a result, the liver can remove more LDL from the bloodstream, lowering LDL cholesterol levels.
Conventional Approaches to LDL Reduction
Statins: Statins are the most commonly used first-line medicines to lower LDL (“bad”) cholesterol. They reduce cholesterol production in the liver and help the liver remove more LDL from the blood.
Long-term use: Statins are usually taken every day for a long period. Therefore, regularly taking the medicine is important for keeping cholesterol levels under control.
PCSK9 inhibitors: These medicines block the PCSK9 protein, helping the liver remove more LDL cholesterol from the blood. However, they usually need to be given through injections every few weeks.
The Emerging “One-Shot” Approaches
siRNA therapy: Small interfering RNA (siRNA) therapies target the messenger RNA (mRNA) responsible for producing PCSK9, thereby reducing PCSK9 production in liver cells.
This allows LDL receptors to remain available for longer and can produce sustained LDL reduction after infrequent dosing.
Base Editing: An emerging approach uses base-editing technology to make a precise change in the DNA sequence of the PCSK9 gene in liver cells.
Unlike conventional medicines that temporarily inhibit a protein, the aim is to produce a long-lasting or potentially permanent reduction in PCSK9 activity after a single treatment.
Key Facts for Prelims
siRNA vs Base Editing: siRNA silences gene expression at the RNA level, producing a reversible/temporary effect, whereas base editing alters a DNA base directly and is designed to produce a much more durable genetic change.
Base Editing and CRISPR: Base editing is a precision gene-editing approach derived from the CRISPR system that can change specific DNA bases without creating the conventional double-strand DNA breaks associated with many earlier CRISPR approaches.