Marathon: Part - 09

Dr. Ravi P. Agrahari

(PhD from IIT Delhi, Author of Mc Graw Hill
Environmental Ecology, Biodiversity, Climate Change
& Disaster Management)

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Dr. Ravi P. Agrahari
❏ PhD (IIT Delhi),
❏ Director (Purvanchal IAS), Gorakhpur (UP)

❏ Faculty of Science & Technology and Environment

❏ PhD IIT Delhi, Experience of Research Scientist of DST
❏ Last 20 years teaching Experiences with 1000 + Selections

❏ Author of McGraw Hill for Science & Technology (Highly Selling

Book in India) and Environment Book
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 UNIT-IX

Biotechnology

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 1. Genome India Project

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The Genome India Project, a project funded and coordinated by the Department of
Biotechnology (DBT), announced that it had finished sequencing 10,000 Indian genomes.

Led by the Centre for Brain Research at the Indian Institute of Science, Bengaluru, and
involving collaboration with 20 institutions, the project seeks to unravel the genetic landscape
of the Indian population and its implications for disease susceptibility and healthcare.

Key features of the Genome India Project include:

The project involves whole-genome sequencing and data analysis of 10,000 individuals
representing the vast genetic diversity present in India's population. This includes various
endogamous groups contributing to genetic variations and disease susceptibility.

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Objectives:

The primary goal of the Genome India Project is to understand the genetic basis of diseases
prevalent in the Indian population and develop predictive diagnostic markers. By sequencing
a large and diverse cohort, researchers aim to identify genetic variations associated with
diseases such as cardiac arrest, which exhibit higher prevalence rates in India compared to
global averages.

Indian Biological Data Centre (IBDC):

The massive dataset generated by sequencing 10,000 genomes, totaling 8 petabytes of data,
will be stored at the Indian Biological Data Centre (IBDC) in Faridabad. Inaugurated in 2022,
the IBDC serves as India's national repository for life science data, facilitating data sharing and
collaboration among researchers.

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Significance:

Establishing an India-specific genetic database is crucial for addressing healthcare challenges

unique to the Indian population.

Insights gained from the project can aid in the development of personalized medicine,
targeted therapies, and disease prevention strategies tailored to the genetic makeup of
individuals.

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 2. Gene Therapies for Sickle Cell Disease

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The U.S Food and Drug Administration (FDA) has approved two Normal RBCs
gene therapies named Lyfgenia and Casgevy for the treatment of
sickle cell disease.

Sickle Cell Disease (SCD)

1. It is a genetic condition that affects the shape of hemoglobin, the

protein responsible for carrying oxygen in red blood cells.
Abnormal/ Sickled RBCs

2. In SCD, red blood cells become crescent- or "sickle"-shaped due

to abnormal hemoglobin. This altered shape causes the cells to
become rigid and sticky, leading to blockages in the blood vessels
and impairing blood flow to various tissues and organs in the body.

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Lyfgenia

Lyfgenia is a cell-based gene therapy developed by Bluebird Bio for the treatment of sickle cell
disease.

Eligibility: The therapy is approved for people aged 12 years and older.

Treatment Process:
1.The treatment involves removing stem cells from the patient's bone marrow from their blood.

2. These stem cells are genetically modified to produce HbAT87Q, a gene-therapy-derived

hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin
produced by individuals without sickle cell disease.

3. The modified stem cells are then administered to the patient through a one-time, single-dose
infusion.

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Casgevy

Casgevy is a CRISPR Cas9-based gene-edited therapy developed for the treatment of Sickle
cell disease and Thalassaemia.

• Casgevy is a one-time treatment.

• It involves removing stem cells from the patient's bone marrow from their blood using a
process called apheresis, which filters out the blood for different components.

• CRISPR gene editing technology is then used in a laboratory to edit the faulty gene.

• The edited cells are then infused back into the patient, allowing the body to produce
functioning hemoglobin.

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Target Gene:

• The therapy targets a gene called BCL11A, which is crucial for switching from fetal to adult
hemoglobin.

• Note: Fetal hemoglobin, which is naturally present in everyone at birth, does not carry the
same abnormalities as adult hemoglobin.

• The therapy uses the body's own mechanisms to start producing more of this fetal
hemoglobin, alleviating the symptoms of the two conditions.

Significance:
• Casgevy is the first licensed therapy in the world based on the gene editing technology
Crispr-Cas9, which earned its innovators a Nobel Prize in 2020.

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 3. ICMR conducts the Truenat Test

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Truenat test

• It is conducted with portable, chip-based and battery-operated machine, developed by

Molbio Diagnostics Private Limited in Goa.

• Originally designed for rapid Tuberculosis (TB) detection. It is a cost-effective alternative to

Polymerase Chain Reaction (PCR) test.

ICMR Endorsement:
• ICMR approves Truenat for infectious disease diagnosis.
• Validated for diseases like COVID-19 and Hepatitis.

Truenat for Nipah and Biosafety Levels (BSL):

• Truenat authorized for Nipah diagnosis in hospitals with BSL 2 level labs.
• Biosafety levels determine necessary protective measures in laboratories.
• Ranges from BSL-1 to BSL-4, with BSL-4 offering maximum containment.

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Indian Council of Medical Research (ICMR):

• Apex body for biomedical research in India.

• Established in 1911 as Indian Research Fund Association (IRFA), renamed ICMR in 1949.
• Governed by the Union Health Minister and supported by a scientific advisory board.
• Funded by the Government of India through the Department of Health Research, Ministry of
Health and Family Welfare.

ICMR Initiatives:

• Establishment of Clinical Trials Registry – India in 2007.

• Serves as the national registry for clinical trials.
• Promotes transparency and accountability in clinical research.

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 5. Stem Cell Therapy

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• Delhi High Court permitted two children with Autism Spectrum Disorder (ASD) to undergo
stem cell therapy for their condition.

• Stem cell therapy is a form of regenerative medicine aimed at repairing damaged cells,
reducing inflammation, and modulating the immune system.

Understanding Stem Cells:

• Stem cells are the origin cells from which all other cells with specialized functions are
generated.

• They have the potential to divide and differentiate into various cell types, such as blood
cells, brain cells, bone cells, and muscle cells.

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Sources of Stem Cells:
1. Embryonic Stem Cells (ESCs)
1. Derived from early-stage embryos.
2. Have the potential to become any cell type in the body.
3. Ethically controversial and strictly regulated in many countries.

2. Induced Pluripotent Stem Cells (iPSCs)

1. Adult cells reprogrammed to behave like embryonic stem cells.
2. Can be generated from a patient’s own cells, reducing the risk of rejection.

3. Adult Stem Cells

1. Found in specific tissues and organs throughout the body.
2. Play a role in tissue maintenance and repair.
3. Examples include hematopoietic stem cells (found in bone marrow) and mesenchymal
stem cells (found in various tissues).

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Applications of Stem Cell Therapy:
1. Regenerative Medicine:
1. Repairing or replacing damaged tissues and organs, such as heart muscle, cartilage, or
nerve cells.

2. Treatment of Chronic Diseases:

1. Exploring potential treatments for conditions like diabetes, Parkinson’s disease,
Alzheimer’s disease, and spinal cord injuries.

3. Immune Disorders:
1. Modifying or enhancing the immune system to fight cancer or autoimmune diseases.

4. Orthopedics:
1. Treating orthopedic injuries and conditions like osteoarthritis.

5. Cosmetic Procedures:
1. Using stem cells for procedures like facial rejuvenation.
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 6. Cell-free DNA

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Cell-free DNA

• cfDNA refers to DNA fragments found outside of cells, present in various body fluids.
• It carries genetic information and offers insights into an individual's health status and
potential diseases.

• Recent advancements have highlighted its significance in disease detection, diagnosis, and
treatment.

Understanding cfDNA:
• cfDNA fragments are released into the extracellular environment due to cellular processes
like cell death.

• It has been studied since 1948, but its practical applications have been realized only in the
last two decades.

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Applications of cfDNA:

1. Non-Invasive Prenatal Testing (NIPT):

1. Utilized for screening chromosomal abnormalities in developing fetuses, such as Down

syndrome.
2. Replaces invasive procedures like amniocentesis, reducing risks for expectant mothers
and fetuses.
3. Analysis of cfDNA in maternal blood provides crucial genetic health information about
the fetus.

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2. Early Cancer Detection:

1. Enables identification of cancers at their initial stages for timely treatment.

2. The 'GEMINI' test utilizes cfDNA sequencing to detect lung cancer with high accuracy.
3. Combined with existing methods, cfDNA analysis enhances overall cancer detection
rates.

3. Monitoring Organ Transplants:

1. Donor-derived cfDNA offers a promising approach to monitor the health and acceptance
of transplanted organs.
2. Fluctuations in cfDNA levels can indicate organ rejection or acceptance before other
markers become evident.
3. Early detection of rejection allows for timely intervention and improved outcomes in
organ transplantation.

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 7. Anthrobots

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• Anthrobots are innovative bio-robots developed using human tracheal cells, exhibiting
remarkable self-assembly capabilities and biological functionalities.

Key Features of Anthrobots:

1. Anthrobots are constructed from human tracheal cells, derived from the lining of the
bronchi and trachea.

2. These cells are specialized epithelial cells responsible for producing mucus to maintain
the functionality of the airways.

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Functionalities:
• Anthrobots exhibit the ability to move and heal neurons within a laboratory setting,
showcasing their potential for dynamic biological interactions.
• Anthrobots can merge to form larger structures known as "superbots," which have
demonstrated the ability to encourage the growth of neurons.

Applications:
• Regenerative Medicine: Anthrobots hold promise for tissue regeneration and repair,
offering novel approaches for addressing wounds and injuries.

• Disease Treatment: Their ability to interact with neurons opens avenues for neurological
disorder treatments and drug delivery systems.

• Wound Healing: Anthrobots may facilitate accelerated wound healing by promoting tissue
regeneration and modulating cellular responses.

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 8. CAR-T Cell Therapy

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India recently approved CAR-T cell therapy, marking a significant milestone in the
country’s
healthcare landscape.

What is CAR T-cell therapy?

It is a type of treatment in which a patient’s T cells (a type of immune cell) are changed in the
laboratory so they will bind to cancer cells and kill them.

• CAR-T cells are a new form of, immunotherapy, itself a fledgling branch of cancer treatment.
• It entails re-engineering the body's T immune cells with some genetic material so that they
selectively target cancer cells for destruction.

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• Working: In this therapy, Blood from a vein in the patient’s arm flows through a tube to an
apheresis machine (not shown), which removes the white blood cells, including the T cells,
and sends the rest of the blood back to the patient.

• Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted
into the T cells in the laboratory.

• Millions of CAR T cells are grown in the laboratory and then given to the patient by infusion.
The CAR T cells are able to bind to an antigen on the cancer cells and kill them.

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 9. Three Parent Baby: Mitochondrial
Replacement Therapy

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The recent announcement of a baby's birth in the UK, carrying DNA from three parents,
has ignited curiosity and prompted discussions regarding the scientific breakthrough
responsible for this remarkable milestone.
What is Mitochondria?

• Membrane-bound organelles present in the cells of most eukaryotic organisms are called Mitochondria.
• Function: Often referred to as the "powerhouses" of cells due to their role in energy production.
• Energy Production: Generate the majority of the cell's energy in the form of adenosine triphosphate (ATP)
through cellular respiration.
• Metabolism: Convert energy from carbohydrates, fats, and proteins into ATP, which fuels cellular processes.
• Cell Signaling: Participate in cell signaling pathways, influencing processes like cell growth, differentiation, and
apoptosis.

Inheritance and Mitochondrial DNA (mtDNA)

• mtDNA: Mitochondria have their own DNA, encoding a small number of essential proteins.
• Maternal Inheritance: In most animals, mtDNA is inherited solely from the mother.
• Implications: Mutations in mtDNA can lead to mitochondrial disorders and various health conditions.

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Mitochondrial Donation Treatment (MDT) / Mitochondrial Replacement Therapy (MRT)

• Purpose: Developed to address the issue of mitochondrial diseases, MDT/MRT is an advanced In Vitro
Fertilization (IVF) technique.
• Objective: Ensure that the baby inherits healthy mitochondria while carrying the genetic material from
both biological parents.

The Scientific Process:

1. Identifying Suitable Candidates:

1. Targeted for couples desiring their genetic child but wish to avoid using a donor egg.
2. Selection of Donor and Biological Parents:
1. Biological Mother: Provides eggs, but she carries a mitochondrial disease.
2. Biological Father: Contributes sperm.
3. Donor: Another female with healthy mitochondria is selected separately.
3. Mitochondrial Replacement:
1. Genetic material (DNA) from the donor's egg is extracted.
2. The donor egg's nucleus is removed, leaving behind healthy mitochondria.

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Dr. Ravi P. Agrahari’s Classes (Science & Technology + Environment): available @Purvanchal IAS App
 1. The nucleus of the donor egg is then replaced with the genetic material from the biological
parents.
2. Resulting in an embryo with the parents' DNA and the donor's mitochondria.

4. Implantation and Pregnancy:

1. The modified embryo is implanted into the uterus of the biological mother.
2. The pregnancy proceeds to full term, leading to the birth of a baby free from the mother's
mitochondrial disease.

MDT/MRT offers hope to couples affected by mitochondrial diseases, allowing them to have
healthy biological children while avoiding the transmission of these disorders. The procedure
involves a meticulous process of mitochondrial replacement, resulting in the birth of a disease-free
baby.

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 THANKYOU

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