In this SlideShare, we'll be diving into Epigenetics and the unexplored approaches in therapeutics. Epigenetics refers to external modifications to DNA that turn genes ‘on’ or ‘off.’ These modifications do not change the DNA sequence itself, but instead, they alter the physical structure of DNA, which affects how our cells ‘read’ genes. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.

1. Exploring New Approaches in Therapeutics
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Epigenetics & Gene Control
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2. Epigenetics & Gene Control
Contents Overview
• Defining Epigenetics
• Nature vs Nurture
• Basics of Gene Expression
• Targeting the Chromosome
for Gene Control
• Epigenetic Methods
• Potential in Therapeutics
• Case Studies
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3. What is Epigenetics?
Source: https://www.livescience.com/37703-epigenetics.html
Epigenetics means ‘above’ or
‘on top of’ genetics.
It studies how our DNA interacts
with other molecules found within
our cells which can ‘activate’ or
‘deactivate’ genes.
In this case, epigenetics refers to
external modifications to DNA that
turn genes ‘on’ or ‘off.’ This affects
how cells read the genes.
Epigenetic modifications do not change the
DNA sequence itself, but instead, they alter
the physical structure of DNA, which affects
how our cells ‘read’ genes.
Credit: WhatIsEpigenetics.com
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4. The human body is made up
of various components, built
from different types of
tissues, and made up of
different cell types.
All the different types of cells
(blood cells, nerve cells, skin
cells, etc.) share the same DNA.
What sets them apart are the
unique epigenetic markers on
our DNA.
Epigenetics Explained
Source: https://genetics.thetech.org/ask-a-geneticist/epigenetics-and-cell-types
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Our genes are expressed differently (turned
‘on’ or ‘off’) by epigenetic markers, which
creates the different cell types.
Credit: The Tech Interactive

5. Nature vs Nurture
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Example: identical twins (who share similar genes) are separated and raised in different
environments, grow to become two very different persons. ‘Nature vs nurture’ paves the way to a
deeper related subject, known as ‘epigenetics’ – influencing how our genes are expressed.
Environmental Variables
• Better economy
• Crime-free
neighbourhood
• Strong support
• Access to better
education & job
prospects
• Better diet & health
routine
Environmental Variables
• Lower economy
• Crime-ridden
neighbourhood
• Poor support
• Lack access to good
education & job
prospects
• Poor diet & health
routine

6. Gene Expression
From Transcription to Translation
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7. Overview of Gene Expression
Source: https://www.yourgenome.org/facts/what-is-gene-expression
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Activation
‘On/Off’ switch to
control when
proteins are
made.
Output
Volume control that
can increase or
decrease the
number of proteins
made.
Gene expression is the process
by which the instructions in our
DNA are converted into
functional products, such as a
proteins.
It is a highly regulated process that
allows our cells to respond to its
changing environment, functioning
both as ‘on/off’ switch, as well as a
volume control.

8. Transcription is when the DNA
in a gene is copied to
produce an RNA transcript
called a messenger RNA
(mRNA).
During transcription, several
enzymes unwind DNA to provide
access to an enzyme called RNA
polymerase which uses
available bases from the
nucleus of the cell to form the
mRNA.
Step 1: Transcription
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Source: https://www.yourgenome.org/facts/what-is-gene-expression
Credit: Genome Research Ltd.

9. Step 2: Translation
Translation occurs when the
formed mRNA enters protein-
making factories in the cell,
called ribosomes.
It is read by a carrier molecule
called transfer RNA (tRNA) which
will read the mRNA 3 nucleotide
bases (a codon) at a time. Each
codon specifies a particular amino
acid, a building block of protein
assembled by a ribosomal RNA
(rRNA).
Source: https://www.yourgenome.org/facts/what-is-gene-expression
Credit: Genome Research Ltd.
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10. Gene Control
Leveraging on the Chromosome Structure
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11. DNA ‘Packaging’
Source: https://www.genome.gov/genetics-glossary/Chromatin
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Our DNA is compacted and
packaged (together with
histones) in the nucleus of the
cell as a substance called
‘chromatin’ (the material that
makes up our chromosomes).
For our genes to be expressed,
the chromatin needs to be
‘opened up’ so our DNA’s
instructions can be read.
Credit: National Human Genome Research Institute

12. Basis for Epigenetics
The chromatin regulatory
system is responsible for the
opening and closing of this
chromatin, and hence
impacts which genes
express certain traits.
This is the basis for epigenetics
which seeks to either suppress &
silence, or even enhance &
amplify gene expression.
Source: https://commonfund.nih.gov/epigenomics/figure
Credit: ResearchGate
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13. DNA Methylation / De-Methylation
Source: https://www.livescience.com/37703-epigenetics.html
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One example of an
epigenetic change is DNA
methylation, which is the
addition (or removal) of a
methyl group (a ‘chemical
cap’) from a DNA molecule.
Chemical caps prevent certain
genes from being expressed
entirely.
Credit: AHA Journals

14. Acetylation / De-Acetylation of Histones
Histones are proteins that
DNA wraps around.
Acetylation can ‘relax’ the
histones, making the DNA
more accessible, which
encourages transcription.
Deacetylation of histones, on the
other hand, would ‘squeeze’ the
DNA tightly, preventing it from
being ‘read’ by our cells.
Credit: ResearchGate
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Euchromatin
(lightly packed)
Heterochromatin
(tightly packed)
deacetylation acetylation
Transcription
inhibited/suppressed
Transcription
activated/enhanced
Source: https://www.livescience.com/37703-epigenetics.html

15. Regulatory RNA
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MicroRNAs (miRNAs) are
small, noncoding sequences
that are involved in gene
expression.
Thousands of miRNAs are
known, and the extent of
their involvement in
epigenetic regulation is an
area of ongoing research.
Credit: EU-CardioRNA
Source: https://www.nature.com/scitable/topicpage/small-non-coding-rna-and-gene-expression-1078/

16. Epigenetic Therapy
Influencing Epigenetic Pathways Directly
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17. Influencing Epigenetic Pathways for Therapy
Source: https://commonfund.nih.gov/epigenomics/figure
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Many diseases,
including cancer,
heart disease,
diabetes, and
mental illnesses are
influenced by
epigenetic
mechanisms.
Epigenetic therapy
offers a potential way to
influence those
pathways directly.

18. Examples of Epigenetic Therapy
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CANCER
Mostly caused by
deactivation of antitumor
systems, and activation of
oncogenes. Epigenetic
therapy seeks to reverse the
process by influencing
patient cells to express more
antitumor activity.
DIABETES
Methylation of certain genes
cause type 2 diabetes
mellitus. Repressed genes
hinders the patient’s ability
to regulate blood sugar
transport. One approach to
epigenetic therapy is to
inhibit methylation.
CARDIAC DYSFUNCTION
Several cardiac dysfunctions
are linked to methylation
patterns of cytosine.
Regulatory RNA therapy is
being investigated. Primary
area of research is using
epigenetic methods to
increase tissue regeneration.

19. Gene Traffic ControlTM by Foghorn Therapeutics
The Gene Traffic ControlTM
Product Platform can
precisely target and
manipulate the chromatin
regulatory system to
develop therapies.
Currently in pre-clinical stage,
GTCTM is rapidly advancing over
10 programs across a wide range
of cancers and is beginning to
explore other diseases.
Credit: Foghorn Therapeutics
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Source: https://foghorntx.com/platform/

20. Treatment of Rare Blood Cancers by Imago BioSciences
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Imago is focused on LSD1 (short for ‘lysine-specific demethylase 1’),
that removes methyl groups from lysines on histones and other
chromatin-bound proteins regulating transcription.
The presence or absence of these ‘methyl marks’ at specific sites on
proteins helps determine the properties and fate of blood cells.
Credit: Imago Biosciences
Source: https://www.imagobio.com/research/scientific-vision/

21. • Epigenetics studies how our DNA interacts with other molecules
found within our cells which can ‘activate’ or ‘deactivate’ genes.
• Unlike gene therapy, which works to alter the DNA sequence
(having inherent side-effects), epigenetic therapy focuses on
changes in DNA expression, making it reversible and cost-
effective.
• Key epigenetic factors include methylation/demethylation of DNA,
histone modifications (acetylation/deacetylation) and regulatory
RNAs.
• Epigenetic approaches in therapy, seeks to either suppress and
silence, or even enhance and amplify gene expression to treat
diseases.
Conclusion
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22. By xeraya capital
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www.xeraya.com
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