2. PHARMACEUTICALS

3. BiopharmaceuticalsBiopharmaceuticals
 are large biological molecules known as
proteins and these usually target the underlying
mechanisms and pathways of a malady.
 are large biological molecules known as
proteins and these usually target the underlying
mechanisms and pathways of a malady.

4. Biopharmaceuticals are protein-
based and may either be derived
from genetically altered bacteria or
fungi (also called biotech drugs), or
may come from blood and blood
plasmaproducts (usually referred to
as biologics).
Biopharmaceuticals are protein-
based and may either be derived
from genetically altered bacteria or
fungi (also called biotech drugs), or
may come from blood and blood
plasmaproducts (usually referred to
as biologics).

5. How Biopharmaceuticals are produced??How Biopharmaceuticals are produced??

6. Examples (Biopharmaceuticals)
Enbrel, Aranesp, Epogen, Neupogen,
Gaminex, recombinant human insulin, and
human growth hormone.
Prospects
Biopharmaceutical products represent a
diverse group of products that include
proteins, peptides, nucleic acids, whole cells,
viral particles and vaccines.

8. The use of
recombinant
DNA technology
to modify
Escherichia coli
bacteria to
produce human
insulin.
The use of
recombinant
DNA technology
to modify
Escherichia coli
bacteria to
produce human
insulin.

9. Insulin Crystals
a) Genetic researchers produced artificial genes
for each of the two protein chains that
comprise the insulin molecule.
b) The artificial genes were then inserted into
plasmids among a group of genes that are
activated by lactose. Thus, the insulin producing
genes were also activated by lactose.
c) The recombinant plasmids were inserted into
Escherichia coli bacteria, which were "induced
to produce 100,000 molecules of either chain A
or chain B human insulin.
d) The two protein chains were then combined to
produce insulin molecules.
a) Genetic researchers produced artificial genes
for each of the two protein chains that
comprise the insulin molecule.
b) The artificial genes were then inserted into
plasmids among a group of genes that are
activated by lactose. Thus, the insulin producing
genes were also activated by lactose.
c) The recombinant plasmids were inserted into
Escherichia coli bacteria, which were "induced
to produce 100,000 molecules of either chain A
or chain B human insulin.
d) The two protein chains were then combined to
produce insulin molecules.

10. Human Growth Hormones
Production of human growth hormone is done by
inserting DNA coding for human growth hormone
into a plasmid that was implanted in Escherichia
coli bacteria.
The gene that was inserted into the plasmid was
created by reverse transcription of the mRNA found
in pituitary glands to complementary DNA.

11. Human Blood Clotting Factors
 Clotting factors isolated from blood are used to treat
some hereditary bleeding disorders such as
hemophilia.
 Human blood clotting factors were produced from
donated blood that was inadequately screened for
HIV. Thus, HIV infection posed a significant danger to
patients with hemophilia who received human blood
clotting factors.
 In this biotechnological procedure, the human gene
that codes for the blood-clotting protein is transferred
to hamster cells grown in tissue culture, which then
produce factor VIII for use by hemophiliacs.

12. Transgenic Farm Animals
Recombinant DNA techniques have
also been employed to create
transgenic farm animals that can
produce pharmaceutical products for
use in humans.

13. For instance, pigs that
produce human
hemoglobin have been
created.
While blood from such
pigs could not be
employed directly for
transfusion to humans,
the hemoglobin could
be refined and
employed to
manufacture a blood
substitute.

14. What are Edible Vaccines?
Edible Vaccines are antigenic proteins that are
genetically engineered into a consumable crop.
 The idea is that the crop food product contains the
protein which is derived from some disease causing
pathogen.
People eat the crop, the food is digested, and some of
the protein makes its way into the blood stream. Get
enough of this protein into the blood stream and it
causes an immune response.
This immune response would now neutralize the
pathogen should the person ever encounter it in the
future.

15. a) Avidin
Avidin is a glycoprotein found in avian, reptilian and amphibian
egg white. It is used primarily as a diagnostic reagent.
b) b-Glucuronidase
GUS (b-glucuronidase; b-d-glucuronide glucuronosohydrolase) is
a homotetrameric hydrolase (68 kDa/subunit) that cleaves b-
linked terminal glucuronic acids in mono and oligo-saccharides
and phenols. GUS is widely used as a visual marker in
transgenic plant research.
c) Trypsin
Maize-derived trypsin, a more recent introduction, has a significant
demand.
Products in MarketProducts in Market

16. Plant-derived Pharmaceuticals
Molecular Farming describes growing and
harvesting genetically modified crops, with the
object of producing not foodstuffs but
pharmaceuticals.
(1) Parental therapeutics and pharmaceutical
intermediates,
(2) Industrial proteins (e.g., enzymes),
(3) Monoclonal antibodies (MAbs), and
(4) Antigens for edible vaccines

17. Genes from other sources
(microorganisms) are sliced into
plant’s genetic apparatus
(genome).
During normal growth these
modified plants synthesize
useful compounds, which are
then extracted from the crop.

18. Product Closed to Market
Aprotinin
 Aprotinin is a protein that inhibits serine
proteases (including trypsin, chymotrypsin,
kallikrein, and pepsin). This activity is known to
modulate and lessen the systemic inflammatory
response (SIR) associated with cardiopulmonary
bypass surgery, which translates into a
decreased need for blood transfusions, reduced
bleeding, and decreased re-exploration for
bleeding.

19. Pharmacogenomics
The study of how the genetic inheritance of an
individual affects his/her body's response to
drugs.
Environment, diet, age, lifestyle, and state of
health all can influence a person's response to
medicines, but understanding an individual's
genetic makeup is thought to be the key to
creating personalized drugs with greater
efficacy and safety.
The study of how the genetic inheritance of an
individual affects his/her body's response to
drugs.
Environment, diet, age, lifestyle, and state of
health all can influence a person's response to
medicines, but understanding an individual's
genetic makeup is thought to be the key to
creating personalized drugs with greater
efficacy and safety.

20. The aim of Pharmacogenetics is to find the
most suitable therapy for a specific individual
or group of people, on the basis of the
genetic characteristics of the same. These
studies are especially useful in the clinical
experimentation of new medicines, as they
help to select the most suitable sample of
patients, establish the appropriate dosages
and, as a consequence, minimize collateral
effects.

21. Pharmacogenomics
Pharmacogenomics is being used for all
critical illnesses like cancer, cardio vascular
disorders, HIV, tuberculosis, asthma, and
diabetes.
In cancer treatment, pharmacogenomics
tests are used to identify which patient will
have toxicity from commonly used cancer
drugs and identify which patient will not
respond to commonly used cancer drug.

22. GENETIC TESTING

23. Genetic TestingGenetic Testing
 involves the direct examination of the
DNA molecule itself. A scientist scans a
patient's DNA sample for mutated
sequences.
Genetic testing is done for a particular
condition where an individual is suspected
of being at increased risk due to their family
or the result of a genetic screening test
 involves the direct examination of the
DNA molecule itself. A scientist scans a
patient's DNA sample for mutated
sequences.
Genetic testing is done for a particular
condition where an individual is suspected
of being at increased risk due to their family
or the result of a genetic screening test

24. When testing the DNA, it is extracted from the tissue, cut into pieces by chemical
‘scissors’ and then the pieces are separated on a gel. The piece of DNA of interest that
contains a particular gene can be selected from the20,000 or so genes in an
individual’s DNA using a special chemical ‘probe’.

25. Uses of Genetic Testing

26. • Diagnosis- A direct gene test can be used to diagnose a
genetic condition. This can be very useful when the clinical
picture is not clear.
The two fragments of DNA represent the faulty
gene copy and the working gene copy. The bands
are heavier from persons A and C as there are two
copies of the same gene at each band. Person A
has two copies of the faulty gene; person B has one
faulty copy and one working copy (ie. a carrier of
the faulty gene) and person C has two copies of the
working form of the gene.

27. Genetic Carrier Screening
• The term ‘genetic carrier screening’ is used to
describe direct gene testing applied to a
whole population or to a defined group.
• For example, genetic carrier screening may be
available for people in the population who
have no personal or family history of a
condition but who have a greater than
average chance of carrying a particular faulty
gene due to their ancestry.

28. Newborn Screening
• The blood sample is taken by a heel-prick
before the baby leaves hospital, or for home
births, on about day 4, and is sent to a special
laboratory.
• The detection of a faulty gene in a person with a
family history of a particular condition, but who
currently has no symptoms of that condition,
means that that person will certainly develop the
condition in later life.
Presymptomatic Genetic Testing

29. Predictive Genetic Testing
• Sometimes the detection of the faulty gene
provides the person with an increased risk
estimate, rather than certainty, that they
will develop a particular condition later in
life.
• Predictive testing for some families is
available for inherited conditions such as an
inherited predisposition to
haemochromatosis or breast cancer.

30. Prenatal Testing
• Indirect gene tracking can be done where
the change in the gene causing a genetic
condition in a family member is not known
but where parents wish to utilize prenatal
testing.
• For example, where parents have a child
with cystic fibrosis (CF) in whom the
mutation(s) causing the condition cannot be
identified.

31. GENE THERAPY
is using "genes as medicine."

32. Gene TherapyGene Therapy
 used for treating, or even curing, genetic
and acquired diseases like cancer and AIDS by
using normal genes to supplement or replace
defective genes or to bolster a normal
function such as immunity.
Gene therapy is being studied in clinical
trials (research studies with people) for many
different types of cancer and for other
diseases.
 used for treating, or even curing, genetic
and acquired diseases like cancer and AIDS by
using normal genes to supplement or replace
defective genes or to bolster a normal
function such as immunity.
Gene therapy is being studied in clinical
trials (research studies with people) for many
different types of cancer and for other
diseases.

33. Two ways of implementing the treatment:
1. Ex vivo (outside the body)
 Cells from the patient's blood or bone marrow are
removed and grown in the laboratory. They are then
exposed to a virus carrying the desired gene. The virus
enters the cells, and the desired gene becomes part of
the DNA of the cells. The cells are allowed to grow in
the laboratory before being returned to the patient by
injection into a vein.
2. In vivo (inside the body)
 No cells are removed from the patient's body. Instead,
vectors are used to deliver the desired gene to cells in
the patient's body.
1. Ex vivo (outside the body)
 Cells from the patient's blood or bone marrow are
removed and grown in the laboratory. They are then
exposed to a virus carrying the desired gene. The virus
enters the cells, and the desired gene becomes part of
the DNA of the cells. The cells are allowed to grow in
the laboratory before being returned to the patient by
injection into a vein.
2. In vivo (inside the body)
 No cells are removed from the patient's body. Instead,
vectors are used to deliver the desired gene to cells in
the patient's body.

34.  Today, nearly 75 percent of all clinical
trials involving gene therapy are aimed at
treatments for cancer and acquired
immunodeficiency syndrome (AIDS).
 Other new gene therapy projects are
targeted at conditions such as heart disease,
diabetes mellitus, arthritis, and Alzheimer's
disease, all of which involve genetic
susceptibility to illness.

35. Researchers are testing several approaches to
gene therapy, including:
Researchers are testing several approaches to
gene therapy, including:
Replacing a mutated gene that causes disease
with a healthy copy of the gene.
Inactivating, or “knocking out,” a mutated gene
that is functioning improperly.
Introducing a new gene into the body to help
fight a disease.
Replacing a mutated gene that causes disease
with a healthy copy of the gene.
Inactivating, or “knocking out,” a mutated gene
that is functioning improperly.
Introducing a new gene into the body to help
fight a disease.

36.  Another application for gene therapy is in
treating X-linked severe combined
immunodeficiency (X-SCID), a disease where a
baby lacks both T and B cells of the immune
system and is vulnerable to infections.
 The current treatment is bone marrow
transplant from a matched sibling, which is not
always possible or effective in the long term.

37. Applications of Biotechnology
on Cancer

38. Cancer is a group of diseases characterized by
uncontrolled cell division leading to growth of
abnormal tissue.
 It is believed that cancers arise from both
genetic and environmental factors that lead to
aberrant growth regulation of a stem cell
population, or by the dedifferentiation of
more mature cell types.

39.  When normal cells are damaged or old they
undergo apoptosis (programmed cell death) ;
cancer cells, however, avoid apoptosis.

40. Diagnosis
a) Biopsy- It requires the removal of cells
and/or pieces of tissue for examination by
a pathologist.
b) Cancer Screening- is the widespread uses
of tests to detect cancers in the
population. If signs of cancer are detected,
more definitive and invasive follow up
tests are performed to confirm the
diagnosis.

41. The future of cancer treatment lies in so-
called targeted therapeutics. This approach
uses advanced cell lines and engineered
organisms to locate and attack defective
molecules. Using gene knockdowns and
knockouts, signal transduction knowledge,
and more, today's researchers work toward
treatment concoctions that fight cancer.

42. Cell Signaling Technology
To observe the intricate structures and
processes carried out within cell walls,
biotechnology researchers use specialized
tools that compare chemical reactions in
normal cells with those that take place in
mutated, cancerous cells.
Cell signaling processes entail the specific
chemical pathways that trigger the DNA
transcription processes that give rise to
mutations.

43. Gene Expression Analysis
• Part of understanding which chemical
pathways give rise to cancerous cells is
knowing which DNA genes trigger the
chemical pathway.
• To figure this out, biotechnologists
examine how the various genes contained
in a DNA molecule work together to create
the signal pathways within a cell.

44. Gene Suppression
 Gene-suppression techniques involve
altering how RNA molecules carry out a
cell's genetic instructions.
 Biotechnology methods employ an RNA
interference gene type that's capable of
shutting down a particular gene's
instructions and its resulting chemical
processes in a cancerous cell.

45. Array Update
• Given all of the discoveries that show
genetic links to some forms of cancer,
researchers want to explore how genes
work together and what proteins they
produce.
• Rather than looking at genes or proteins
one by one, scientists look simultaneously
at hundreds to several thousands with
microarrays.

46. Gene Knockout
 To determine how a gene works, scientists can turn
it off in a whole animal and see what happens, as in a
knockout mouse.
 "A knockout mouse is pretty straightforward: take
out a gene that you suspect might be involved in
cancer and examine the resulting phenotype.
 Knocking out either a proto-oncogene or a tumor
suppressor gene, for example, could make a mouse
more susceptible to developing tumors, potentially
allowing tumors to arise more quickly and grow
faster.

47. Exploiting Interference
• During the mid 1990s, researchers
discovered RNA interference (RNAi), which
can knock down a specific gene.
• Double stranded RNA sets off a process
that cuts up homologous messenger RNA.
Consequently, the gene that made that
mRNA gets effectively shut down.
• RNA interference provides lots of angles for
cancer research.