Topic 69: Biology – Cell, Physiology, Biotech,

Q: What is CRISPR-Cas9? Who developed it and what is its first approved therapeutic application?

**CRISPR-Cas9** is a **gene editing technology** derived from a bacterial immune system. A guide RNA directs the **Cas9 protein** to cut DNA at a precise target sequence, enabling gene insertion, deletion, or replacement. Developed by **Jennifer Doudna and Emmanuelle Charpentier** (Nobel Prize Chemistry, 2020). First approved therapeutic application: **CASGEVY** (CTX001) — approved by **FDA in December 2023** for **sickle cell disease** and beta-thalassaemia. India's FelUDA used CRISPR for COVID-19 diagnostics (DCGI approved, 2021).

Study Material

Paper Paper II

Unit 2

1. Cell — Basic Unit of Life - Prokaryotic cells (bacteria, archaea) lack a membrane-bound nucleus and organelles - Eukaryotic cells (plants, animals, fungi) have a true nucleus and membrane-bound organelles - Eukaryotic organelles include mitochondria, endoplasmic reticulum, and Golgi apparatus
2. Photosynthesis - Equation: 6CO₂ + 6H₂O + light → C₆H₁₂O₆ + 6O₂ - Occurs in chloroplasts — light-dependent reactions in thylakoids; Calvin cycle (dark reactions) in stroma - Chlorophyll a and b absorb red and blue light; reflect green
3. Human Digestive System - Mouth (amylase — starch) → stomach (pepsin, HCl — proteins) → small intestine (lipase — fats; trypsin — proteins; bile from liver) → large intestine (water absorption) - Insulin from beta cells of pancreas lowers blood glucose - Glucagon from alpha cells raises blood glucose
4. Blood Groups — ABO System - Discovered by Karl Landsteiner, 1900 (Nobel 1930) - A (antigen A, antibody b), B (antigen B, antibody a), AB (both antigens, no antibody — "universal recipient"), O (no antigens, both antibodies — "universal donor") - Rh incompatibility in pregnancy causes haemolytic disease of the newborn
5. Immunity - Innate immunity — non-specific: skin barrier, phagocytes, inflammation, fever - Adaptive immunity — specific: B lymphocytes produce antibodies (humoral); T lymphocytes attack infected cells (cell-mediated) - Memory cells enable faster response on re-exposure — the basis of vaccination
6. Vaccines - Introduce weakened/killed pathogens or antigens to prime immune memory without causing disease - Types: Live attenuated (BCG for TB, OPV for polio), Inactivated (IPV, flu), Subunit (Hepatitis B) - mRNA vaccines (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) — first approved for COVID-19 in December 2020
7. CRISPR-Cas9 - Derived from a bacterial immune system; repurposed as a gene editing tool - Developed by Jennifer Doudna and Emmanuelle Charpentier — Nobel Prize Chemistry 2020 - A guide RNA directs Cas9 protein to cut DNA at a specific sequence, enabling insertion, deletion, or replacement of genes
8. Genetically Modified Organisms (GMOs) - Organisms whose DNA is altered using genetic engineering - Bt cotton (Bacillus thuringiensis toxin gene) — India's first approved GMO crop (2002); ~90% of India's cotton cultivation; reduced insecticide use by 40% - Controversy: Bt brinjal — GEAC approved 2010, moratorium imposed; Golden Rice stalled due to opposition
9. Fermentation - Anaerobic breakdown of organic matter by microbes - Alcoholic fermentation: C₆H₁₂O₆ → 2C₂H₅OH + 2CO₂ (yeast *Saccharomyces cerevisiae*) — beer, wine, bioethanol, bread - Lactic acid fermentation: glucose → lactic acid (bacteria) — yogurt, cheese, silage
10. Biotechnology - WHO definition: application of biological systems and organisms to develop products and processes - Traditional biotech: selective breeding, fermentation; Modern biotech: recombinant DNA, gene editing, tissue culture, bioreactors - India's biotech sector valued at $137 billion (2023); target $300 billion by 2030 under National Biotechnology Strategy
11. Artificial Organs and Biomedical Devices - Artificial heart (total artificial heart — SynCardia TAH); ventricular assist devices (VAD) - Cochlear implant — electric stimulation of auditory nerve for hearing restoration - 3D-printed organs (bioprinting using living cells — research stage for kidney, liver); artificial kidney (dialysis machine)
12. Microbes and Human Welfare - Lactobacillus (curd/yogurt); E. coli (model organism; recombinant insulin production); Rhizobium (nitrogen fixation in legumes) - Penicillium notatum (penicillin antibiotic); Aspergillus niger (citric acid, vinegar) - Viruses used beneficially in gene therapy as adenoviral vectors
13. Human Genome - Contains ~3.2 billion base pairs encoding ~20,000–25,000 genes - Human Genome Project (HGP) — completed April 2003 (13-year, $3 billion; USA/UK/France/Germany/Japan/China); applications: disease gene identification, personalised medicine, pharmacogenomics - India's Genome India Initiative (launched 2019) — sequencing 10,000 Indian genomes for population-specific disease research

Key facts

Photosynthesis — Equation: 6CO₂ + 6H₂O + light → C₆H₁₂O₆ + 6O₂ — Occurs in chloroplasts
Blood Groups — ABO System — Discovered by Karl Landsteiner, 1900 (Nobel 1930)
Vaccines — Introduce weakened/killed pathogens or antigens to prime immune memory without causing disease
CRISPR-Cas9 — Derived from a bacterial immune system; repurposed as a gene editing tool — Developed by Jennifer Doudna and Emmanuelle Charpentier
Genetically Modified Organisms (GMOs) — Organisms whose DNA is altered using genetic engineering — Bt cotton (Bacillus thuringiensis toxin gene)

Key Points at a Glance

1
Cell — Basic Unit of Life
- Prokaryotic cells (bacteria, archaea) lack a membrane-bound nucleus and organelles
- Eukaryotic cells (plants, animals, fungi) have a true nucleus and membrane-bound organelles
- Eukaryotic organelles include mitochondria, endoplasmic reticulum, and Golgi apparatus
2
Photosynthesis
- Equation: 6CO₂ + 6H₂O + light → C₆H₁₂O₆ + 6O₂
- Occurs in chloroplasts — light-dependent reactions in thylakoids; Calvin cycle (dark reactions) in stroma
- Chlorophyll a and b absorb red and blue light; reflect green
3
Human Digestive System
- Mouth (amylase — starch) → stomach (pepsin, HCl — proteins) → small intestine (lipase — fats; trypsin — proteins; bile from liver) → large intestine (water absorption)
- Insulin from beta cells of pancreas lowers blood glucose
- Glucagon from alpha cells raises blood glucose
4
Blood Groups — ABO System
- Discovered by Karl Landsteiner, 1900 (Nobel 1930)
- A (antigen A, antibody b), B (antigen B, antibody a), AB (both antigens, no antibody — "universal recipient"), O (no antigens, both antibodies — "universal donor")
- Rh incompatibility in pregnancy causes haemolytic disease of the newborn
5
Immunity
- Innate immunity — non-specific: skin barrier, phagocytes, inflammation, fever
- Adaptive immunity — specific: B lymphocytes produce antibodies (humoral); T lymphocytes attack infected cells (cell-mediated)
- Memory cells enable faster response on re-exposure — the basis of vaccination
6
Vaccines
- Introduce weakened/killed pathogens or antigens to prime immune memory without causing disease
- Types: Live attenuated (BCG for TB, OPV for polio), Inactivated (IPV, flu), Subunit (Hepatitis B)
- mRNA vaccines (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) — first approved for COVID-19 in December 2020
7
CRISPR-Cas9
- Derived from a bacterial immune system; repurposed as a gene editing tool
- Developed by Jennifer Doudna and Emmanuelle Charpentier — Nobel Prize Chemistry 2020
- A guide RNA directs Cas9 protein to cut DNA at a specific sequence, enabling insertion, deletion, or replacement of genes
8
Genetically Modified Organisms (GMOs)
- Organisms whose DNA is altered using genetic engineering
- Bt cotton (Bacillus thuringiensis toxin gene) — India's first approved GMO crop (2002); ~90% of India's cotton cultivation; reduced insecticide use by 40%
- Controversy: Bt brinjal — GEAC approved 2010, moratorium imposed; Golden Rice stalled due to opposition
9
Fermentation
- Anaerobic breakdown of organic matter by microbes
- Alcoholic fermentation: C₆H₁₂O₆ → 2C₂H₅OH + 2CO₂ (yeast Saccharomyces cerevisiae) — beer, wine, bioethanol, bread
- Lactic acid fermentation: glucose → lactic acid (bacteria) — yogurt, cheese, silage
10
Biotechnology
- WHO definition: application of biological systems and organisms to develop products and processes
- Traditional biotech: selective breeding, fermentation; Modern biotech: recombinant DNA, gene editing, tissue culture, bioreactors
- India's biotech sector valued at $137 billion (2023); target $300 billion by 2030 under National Biotechnology Strategy
11
Artificial Organs and Biomedical Devices
- Artificial heart (total artificial heart — SynCardia TAH); ventricular assist devices (VAD)
- Cochlear implant — electric stimulation of auditory nerve for hearing restoration
- 3D-printed organs (bioprinting using living cells — research stage for kidney, liver); artificial kidney (dialysis machine)
12
Microbes and Human Welfare
- Lactobacillus (curd/yogurt); E. coli (model organism; recombinant insulin production); Rhizobium (nitrogen fixation in legumes)
- Penicillium notatum (penicillin antibiotic); Aspergillus niger (citric acid, vinegar)
- Viruses used beneficially in gene therapy as adenoviral vectors
13
Human Genome
- Contains ~3.2 billion base pairs encoding ~20,000–25,000 genes
- Human Genome Project (HGP) — completed April 2003 (13-year, $3 billion; USA/UK/France/Germany/Japan/China); applications: disease gene identification, personalised medicine, pharmacogenomics
- India's Genome India Initiative (launched 2019) — sequencing 10,000 Indian genomes for population-specific disease research

What does Topic 69 cover in the RPSC Science and Technology syllabus?

Topic 69 covers the biology end of Science and Technology: cell biology, plant and human physiology, food and immunity, microbes and fermentation, biotechnology, genetic engineering, vaccines, CRISPR, mRNA technology and artificial organs. The RPSC official Mains syllabus states that each of the four descriptive papers carries 200 marks, so Science and Technology must be prepared as part of a high-weight Mains paper rather than as a small factual appendix. Topic 69 is the second-highest scoring topic in the S&T unit with 62 marks over 6 exam years. Biology questions in RPSC have progressively modernised — from basic cell biology in 2013 to COVID-19 diagnostics in 2021 and now explicitly including CRISPR, mRNA vaccines, and artificial organs in the 2026 syllabus. These three sub-domains have never been asked in previous exams and are therefore highest-probability for 2026.

Topic distribution strategy: The breadth of Topic 69 (cell → plant physiology → human body → biotech → cutting-edge tech) means the examiner can ask on virtually anything. Focus 70% of preparation on modern biotech (CRISPR, mRNA, GMO, fermentation, artificial organs) and 30% on classic physiology (blood groups, digestion, nutrition, immunity).

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PREDICTED Predicted RAS Questions

Based on PYQ trends and 2026 syllabus analysis

1 5M What is CRISPR-Cas9? Who developed it and what is its first approved therapeutic application? 5 marks · 50 words

Model Answer

CRISPR-Cas9 is a gene editing technology derived from a bacterial immune system. A guide RNA directs the Cas9 protein to cut DNA at a precise target sequence, enabling gene insertion, deletion, or replacement. Developed by Jennifer Doudna and Emmanuelle Charpentier (Nobel Prize Chemistry, 2020). First approved therapeutic application: CASGEVY (CTX001) — approved by FDA in December 2023 for sickle cell disease and beta-thalassaemia. India's FelUDA used CRISPR for COVID-19 diagnostics (DCGI approved, 2021).

~50 words • 5 marks