Why Is It in News?
- CSIR-IGIB (Institute of Genomics & Integrative Biology) has developed India’s first fully indigenous CRISPR-Cas9–based gene editing platform.
- Technology transferred to Serum Institute of India (SII) for Phase II–III clinical trials.
- Using this platform, IGIB developed a curative gene therapy for sickle cell disease (SCD) named Birsa-101 (after Birsa Munda, as SCD is highly prevalent among tribal communities).
- Expected to be significantly cheaper than the US-approved gene therapy Casgevy (USD 2.2 million per patient).
- Phase I trials will be conducted with AIIMS Delhi; manufacturing facility already set up.
Relevance
GS-2 (Health, Governance)
- National SCD Elimination Mission.
- Inclusive tribal health policy.
GS-3 (Science & Technology)
- Biotechnology, genetic engineering, indigenous R&D.
- CRISPR applications and ethical concerns.
GS-1 (Society)
- Tribal health challenges.
- Disease burden in vulnerable populations.
What Is Sickle Cell Disease (SCD)?
- Inherited blood disorder caused by mutation in the HBB gene → defective haemoglobin (HbS).
- Results in:
- Rigid, sickle-shaped RBCs
- Blocked blood vessels
- Pain crises, anaemia, organ failure
- Infections, stroke risk
- India’s tribal belts in MP, Chhattisgarh, Jharkhand, Odisha, Maharashtra, Gujarat have highest burden.
Basics of CRISPR-Cas9 Gene Editing
What is CRISPR-Cas9?
- A bacterial immune-system protein that acts as “genetic scissors”.
- Precisely cuts specific DNA segments → allows correction of disease-causing mutations.
- Awarded the 2020 Nobel Prize for Chemistry.
Indian Improvement
- IGIB scientists created an indigenous Cas9 variant (2016):
- Avoids expensive Western IP.
- Optimised for reduced off-target effects (major global concern).
- Allows editing exactly at the mutation site (curative edit).
What Is Birsa-101 Gene Therapy?
Mechanism
- Directly corrects the defective mutation in HBB gene.
- One-time infusion of edited stem cells.
- Once corrected, the body begins producing normal haemoglobin.
How it differs from Casgevy (US therapy)
| Feature | Birsa-101 (India) | Casgevy (US/UK) |
| Strategy | Corrects the original mutation | Increases fetal haemoglobin (HbF) to bypass defect |
| Technology | Indigenous CRISPR-Cas9 | Licensed CRISPR tech (very expensive) |
| Cost | Expected to be fraction of $2.2 million | $2.2 million per patient |
| Long-term effect | Potential cure | Functional cure but mechanism bypasses root cause |
Why Is This a Major Scientific Breakthrough?
A. Complete Indigenous Development
- All patents held by Indian scientists.
- Avoids global IP licensing → drastically lower cost → scalable for India’s tribal SCD mission.
B. Addresses a Major Public Health Challenge
- SCD affects:
- ~1 in 86 births in certain tribal districts.
- 10–11% carrier prevalence in many Adivasi populations.
- Aligned with National Mission to Eliminate Sickle Cell Anaemia (2023–2030).
C. Global-Standard Gene Editing Platform
- India becomes one of very few countries with:
- Own CRISPR tool
- Own clinical-grade manufacturing
- Capability for gene-editing therapy trials
D. Reduced “Off-Target” Risk
- IGIB Cas9 engineered to minimise unintended edits:
- Off-target mutations can cause cancer, developmental defects, organ damage.
- Many global Cas9 variants unsuitable for therapy due to unpredictable cuts.
What Happens Next?
Clinical Pathway
- Phase I trials (AIIMS Delhi, 2025) → safety, dosing.
- Phase II–III trials (Serum Institute) → efficacy, scalability.
- Regulatory review by CDSCO + DBT + ICMR.
- Integration into national SCD elimination programme after approval.
Industrial Pathway
- IGIB already built GMP-grade manufacturing for clinical batches.
- SII to scale production for national deployment after Phase I.
Wider Scientific Significance
- Positions India in the global gene therapy market (currently dominated by US/EU).
- Opens doors for editing therapies for:
- Thalassemia
- Gaucher’s disease
- Duchenne muscular dystrophy
- Rare genetic disorders (India has 70M affected)
- Establishes a sovereign biotechnological ecosystem:
- Indigenous gene-editing IP
- Indigenous manufacturing
- Indigenous clinical trial pipeline
Challenges Ahead
- Ensuring long-term safety (off-target monitoring for years).
- Cost reduction for mass rollout in rural tribal belts.
- Infrastructure for genetic testing, counselling, and follow-up.
- Ethical and regulatory oversight for gene editing.
