"Gene-editing therapy VERVE-102 targets PCSK9 to permanently lower LDL cholesterol"
PCSK9
liver protein that degrades LDL receptors, raising circulating LDL cholesterol levels.
In vivo gene editing
genetic modification performed directly inside a living patient's body.
Cardiovascular disease (CVD) is the leading cause of death globally and an accelerating public health crisis in India, where premature heart attacks — often striking a decade earlier than in Western populations — are increasingly common. Low-density lipoprotein (LDL) cholesterol is the primary modifiable risk factor: it accumulates in arterial walls, forming hard fatty deposits called plaque, which narrow arteries and precipitate heart attacks and strokes. For decades, statins (HMG-CoA reductase inhibitors) have been the cornerstone of lipid-lowering therapy, reducing the liver's cholesterol synthesis at low cost. However, statins fail a significant subset of patients — particularly those with familial hypercholesterolaemia (FH), an inherited disorder affecting roughly 1 in 250 people — who cannot reach guideline-recommended LDL targets even on maximum doses.
The discovery of PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) as a regulator of LDL metabolism opened a new therapeutic frontier. Scientists observed that individuals with naturally occurring loss-of-function mutations in the PCSK9 gene have persistently lower LDL levels throughout their lives and a markedly reduced risk of coronary heart disease — a compelling natural experiment that validated PCSK9 inhibition as a safe long-term strategy. This biological insight drove the development of injectable PCSK9 monoclonal antibodies and, more recently, oral PCSK9 inhibitors, both of which reduce LDL by 50–60% but require ongoing administration.
PCSK9 is a protein produced by liver cells that normally binds to LDL receptors on the liver's surface and tags them for degradation. Fewer LDL receptors mean the liver clears less LDL from the bloodstream, raising circulating LDL levels. PCSK9 inhibitors — whether injectable monoclonal antibodies or the recently approved oral pill Lipfendra (enlicitide) — block this protein, thereby preserving LDL receptors and dramatically enhancing the liver's LDL-clearance capacity. This mechanism is fundamentally different from statins, which reduce cholesterol production; PCSK9 inhibitors enhance cholesterol clearance. The two approaches are therefore complementary rather than competing.
VERVE-102 represents a third and more radical paradigm: in vivo gene editing. Rather than blocking the PCSK9 protein pharmacologically, VERVE-102 delivers genetic instructions via an intravenous infusion that permanently alters the PCSK9 gene inside liver cells, switching it off at the DNA level. …
What is Cas9 protein that is often mentioned in news?
With reference to hereditary diseases, consider the following statements:
1.Passing on mitochondrial diseases from parent to child can be prevented by mitochondrial replacement therapy (Mitochondrial Replacement) either before or after in vitro fertilization of egg.
2.A child inherits mitochondrial diseases entirely from the mother and not from the father.
Which of the statements given above is/are correct?
In the context of recent advances in human reproductive technology, 'Pronuclear Transfer' is used for
With reference to PCSK9 and its role in cholesterol metabolism, consider the following statements:
1.PCSK9 is a protein produced by the liver that promotes the degradation of LDL receptors on liver cell surfaces.
2.Inhibiting PCSK9 reduces the liver's ability to clear LDL from the bloodstream.
3.Individuals with naturally occurring loss-of-function mutations in the PCSK9 gene tend to have lower LDL levels and reduced coronary heart disease risk.
Which of the statements given above is/are correct?
VERVE-102, recently in news, is best described as which of the following?
Consider the following pairs regarding lipid-lowering therapies and their primary mechanism of action:
1.Statins — Reduce cholesterol production in the liver by inhibiting HMG-CoA reductase
2.PCSK9 monoclonal antibodies — Enhance LDL clearance by preserving LDL receptors on liver cells
3.VERVE-102 — Temporarily block PCSK9 protein activity through repeated infusions
How many of the above pairs are correctly matched?
Assertion (A): A 60% reduction in LDL cholesterol achieved by VERVE-102 in clinical trials can approximately halve a patient's risk of heart attack or stroke.
Reason (R): For every 1 mmol/L reduction in LDL cholesterol, cardiovascular risk falls by approximately 20–22%.
Which of the following is correct?
With reference to the CRISPR-Cas9 system and its applications in medicine, which of the following statements is/are correct?
1.The CRISPR-Cas9 system was originally derived from the natural immune defence mechanism of bacteria against viral infections.
2.In gene inhibition therapy, a gene is introduced whose product blocks the expression of a faulty gene.
3.In vivo gene therapy involves editing cells outside the patient's body before reinfusion.
Select the correct answer using the code below:
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