Score:
9/15
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Topper’s Copy
GS3
Science & Technology
15 marks
“Recent advances in CRISPR technology have enabled the reactivation of silenced genes without cutting DNA by targeting epigenetic markers.”
In this context, explain the role of epigenetic gene silencing in human diseases and critically examine how non–DNA-cutting CRISPR approaches could make gene therapy safer and more ethical, with special reference to sickle cell disease.
Student’s Answer
Evaluation by SuperKalam
Demand of the Question
- Explain the role of epigenetic gene silencing in human diseases
- Critically examine how non–DNA-cutting CRISPR approaches could make gene therapy safer and more ethical
- Special reference to sickle cell disease
What you wrote:
Recent advances (2023-25, Nature, Science) demonstrate CRISPR-based epigenetic editing that can reactivate silenced genes without cutting DNA. This approach offers safer and ethically robust gene therapy, particularly for sickle cell disease (SCD).
CRISPR Approaches Compared
Traditional CRISPR
DNA cut → Permanent Change → High Risk.
Epigenetic CRISPR (dCas9)
NO DNA Cut → HbF Reactivation → Safer Therapy
Recent advances (2023-25, Nature, Science) demonstrate CRISPR-based epigenetic editing that can reactivate silenced genes without cutting DNA. This approach offers safer and ethically robust gene therapy, particularly for sickle cell disease (SCD).
CRISPR Approaches Compared
Traditional CRISPR
DNA cut → Permanent Change → High Risk.
Epigenetic CRISPR (dCas9)
NO DNA Cut → HbF Reactivation → Safer Therapy
Suggestions to improve:
- Could briefly define epigenetics upfront (e.g., "Epigenetics refers to heritable changes in gene expression without altering DNA sequences, primarily through DNA methylation and histone modifications") to ground the reader before jumping into CRISPR comparison.
What you wrote:
Epigenetic Gene Silencing in Human Diseases
(i) 'Epigenetic': Regulation of gene expression without altering DNA sequence.
(ii) key mechanisms: a) DNA methylation b) Histone modification.
(iii) Disease relevance:
a) Cancer: Silencing of tumour suppressor genes
b) Neurodevelopmental disorders.
c) Sickle Cell Disease: Post-birth silencing of fetal haemoglobin (HbF) increases disease severity.
Epigenetic Gene Silencing in Human Diseases
(i) 'Epigenetic': Regulation of gene expression without altering DNA sequence.
(ii) key mechanisms: a) DNA methylation b) Histone modification.
(iii) Disease relevance:
a) Cancer: Silencing of tumour suppressor genes
b) Neurodevelopmental disorders.
c) Sickle Cell Disease: Post-birth silencing of fetal haemoglobin (HbF) increases disease severity.
Suggestions to improve:
- Could explain disease mechanisms with precision (e.g., "In Prader-Willi Syndrome, abnormal methylation patterns silence paternal genes critical for metabolism and behavior, demonstrating how epigenetic errors cause complex developmental disorders").
- Can add how epigenetic silencing differs from genetic mutations (e.g., "Unlike permanent DNA mutations, epigenetic changes are reversible, making them therapeutic targets—such as using demethylating agents like Azacitidine in myelodysplastic syndrome").
What you wrote:
Non-DNA-cutting CRISPR: How it works
1) uses dCas9 (dead Cas9) - binds DNA but does not cut it.
2) Coupled with epigenetic modifiers (demethylases, acetyltransferases).
3) Reverses epigenetic silencing, turning beneficial genes back on.
4) Effects are programmable and potentially reversible.
Application to Sickle Cell Disease
1) SCD caused by abnormal adult haemoglobin (HbS)
2) HbF prevents red blood cell sickling.
3) Epigen Reduces pain crises and transfusion dependence.
Safer & More Ethical
A) Safety
(i) No double-strand DNA breaks → minimal off-target mutations.
(ii) lower risk of oncogenesis and chromosomal rearrangements.
B) Ethical Advantages
(i) Suitable for somatic cell therapy, not germline editing.
(ii) Reversible regulation enhances consent & control.
Non-DNA-cutting CRISPR: How it works
1) uses dCas9 (dead Cas9) - binds DNA but does not cut it.
2) Coupled with epigenetic modifiers (demethylases, acetyltransferases).
3) Reverses epigenetic silencing, turning beneficial genes back on.
4) Effects are programmable and potentially reversible.
Application to Sickle Cell Disease
1) SCD caused by abnormal adult haemoglobin (HbS)
2) HbF prevents red blood cell sickling.
3) Epigen Reduces pain crises and transfusion dependence.
Safer & More Ethical
A) Safety
(i) No double-strand DNA breaks → minimal off-target mutations.
(ii) lower risk of oncogenesis and chromosomal rearrangements.
B) Ethical Advantages
(i) Suitable for somatic cell therapy, not germline editing.
(ii) Reversible regulation enhances consent & control.
Suggestions to improve:
- Could deepen ethical examination (e.g., "While epigenetic CRISPR avoids germline modification concerns, ethical questions remain: Will costly therapies widen healthcare inequities? Should regulatory frameworks like India's Genomic Data Protection Bill mandate affordability clauses?").
- Can reference real-world breakthroughs (e.g., "The FDA-approved Casgevy therapy demonstrates epigenetic reactivation's clinical viability, though its $2.2 million cost raises ethical concerns about equitable access in low-resource settings like India").
What you wrote:
Epigenetic CRISPR represents a paradigm shift in gene therapy, offering safer, reversible, and ethically superior treatment options - especially transformative for diseases like sickle cell anaemia.
Epigenetic CRISPR represents a paradigm shift in gene therapy, offering safer, reversible, and ethically superior treatment options - especially transformative for diseases like sickle cell anaemia.
Suggestions to improve:
- Could highlight future directions (e.g., "India's Genome India Project and collaborative trials under the Department of Biotechnology could leverage epigenetic CRISPR to develop affordable, indigenous SCD therapies, aligning with Universal Health Coverage goals").
- Can stress regulatory need (e.g., "Robust ethical frameworks, such as mandatory long-term safety monitoring and equitable pricing policies, are essential to prevent epigenetic therapies from becoming exclusive to the privileged").
Your answer demonstrates strong conceptual understanding and effective use of visuals. The structure is clear, and you've addressed all three demands. However, the critical examination lacks depth—particularly ethical nuances and real-world examples. Strengthening the analytical layer with specific trials, regulatory contexts, and equity concerns will elevate your response significantly.
Demand of the Question
- Explain the role of epigenetic gene silencing in human diseases
- Critically examine how non–DNA-cutting CRISPR approaches could make gene therapy safer and more ethical
- Special reference to sickle cell disease
What you wrote:
Recent advances (2023-25, Nature, Science) demonstrate CRISPR-based epigenetic editing that can reactivate silenced genes without cutting DNA. This approach offers safer and ethically robust gene therapy, particularly for sickle cell disease (SCD).
CRISPR Approaches Compared
Traditional CRISPR
DNA cut → Permanent Change → High Risk.
Epigenetic CRISPR (dCas9)
NO DNA Cut → HbF Reactivation → Safer Therapy
Recent advances (2023-25, Nature, Science) demonstrate CRISPR-based epigenetic editing that can reactivate silenced genes without cutting DNA. This approach offers safer and ethically robust gene therapy, particularly for sickle cell disease (SCD).
CRISPR Approaches Compared
Traditional CRISPR
DNA cut → Permanent Change → High Risk.
Epigenetic CRISPR (dCas9)
NO DNA Cut → HbF Reactivation → Safer Therapy
Suggestions to improve:
- Could briefly define epigenetics upfront (e.g., "Epigenetics refers to heritable changes in gene expression without altering DNA sequences, primarily through DNA methylation and histone modifications") to ground the reader before jumping into CRISPR comparison.
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