Table of Contents

What is Gene Therapy............................................................................................................................................ 2

Vectors ................................................................................................................................................................ 4
Principle (of Gene Therapy) ................................................................................................................................... 5
Mechanism ............................................................................................................................................................. 5
Viral vectors .................................................................................................................................................... 6
Non-viral vectors……………………………………………………………………………………………………………………………………….7

Types of Gene Therapy..……………………………………………………………………………………………………………………………8

In vivo delivery………………………………………………………………………..……………………………………………………….8

Ex vivo delivery…………………………………………………………………………………………………………………………………9

Examples of Available Gene Therapies……………………………………………………………………………………………………….10

CAR T-Cell therapy…………………………………………………………………………………………………………………………………10

Zolgensma: Gene Therapy for SMA………………………………………………………………………………………………………..11

Luxturna:Gene Therapy for Vision Loss…………………………………………………………………………………………………..12

Bibliography……………………………………………………………………………………………………………………………………………………13

Page 1 of 13
 What is Gene Therapy?

Our bodies are made up of trillions of cells. Most cells contain

genes. Genes are made of DNA. Genes are like instructions to
everything in our bodies.

Figure 1: Gene

They contain the coded instructions for specific proteins.

Differences in the DNA code can result in protein changes, which
makes each person who they are. This includes changing our hair
type and eye colour. Sometimes the genetic instructions have a
change, which could be a spelling mistake or have bits missing. This
can cause a protein to be made incorrectly or not at all, which can
result in a genetic condition. That's where gene therapy comes in.
Gene therapy targets the genes responsible for these conditions. It
may prevent, improve or slow the progression, or even potentially

Page 2 of 13
cure, depending on the condition. Genes decides whether we are
tall or short, light or dark skinned, blue eyes or brown eyes, etc.
What if parts of a gene are defective or missing?

If a gene changes or mutates? It can cause a disease like cancer. The

answer is Gene Therapy.

The scientists can replace the bad gene with the one that is happy,
add a new gene to perform the function of the defective or missing
gene, or they can turn of a problem gene.

Figure 2: Gene Transfer

How do they do it? Say scientists want to add back a healthy copy
of a gene to cells, they need an efficient way to do it. So, scientists
use vectors or vehicles to deliver the gene.

Page 3 of 13
 Vectors/Vehicle for Gene Delivery
The vehicle or the molecule that are used to deliver genes are
called as vectors. For
example, Viruses are one
kind of vector. Scientists
modify a virus to remove
its ability to cause a
disease. The modified virus
can then be used to carry
the healthy gene into a
cell.
Gene therapy can happen on
cells inside the body. Or can
happen on cells outside and
then transplanted back inside
the body. Genes make us who
we are and gene therapy holds
great promise for a healthy
future. It holds the promise
Figure 3: Vectors
to transform medicine and
create options for patients who are living with difficult, and even
incurable, diseases.
Gene therapy generally falls into three introducing a therapeutic
gene, altering the way a gene is processed, or editing a gene
directly. Introducing a functioning copy of the gene will produce the
necessary protein. Altering the way a gene is processed means, for
example, skipping over a mistake. Editing delivers an editing tool to
targeted cells, correcting the genetic instructions to restore protein
production. Gene therapy is a rapidly evolving and exciting form of
treatment. However, it is not always a cure. Long term outcomes
for the benefits and safety are still being studied and understood.

Page 4 of 13
 Principle
The basic principle of gene therapy is that the intrinsic expression of
certain genes in body tissues can be modified to treat genetic
disease. This may involve replacing a defective gene with a
functional version, enhancing the baseline expression level of a
gene or, contrastingly, suppressing the expression of genes that
may contribute to the pathologic process. As we see the advancing
in the field of gene therapy, it is possible that it will soon become
standard treatment available for both interns and surgeons.
The idea of gene therapy is correcting the genetic abnormalities in
a patient, either by replacing or removing them to treat or prevent
disease. This method includes the introduction, alteration or
elimination of genes within an individual 's cells. Gene therapy
often aims to:
1. Gene Therapy has mean to correct an unhealthy gene:
You can replace a gene that is not functioning correctly,
or replace the function with a healthy copy of the same
one.
2. Knock out or inactivate a defective gene: If an
individual has a diseased due to a defect variety of the
gene, gene therapy might be used to knock out that
type.
3. Add a gene to help combat disease: Adding a gene that
will produce a protein or enzyme may counter the
effects of disease.
4. Gene Editing: Methods such as CRISPR-Cas9 allow
precise editing of the DNA within cells. This can correct
mutations at specific locations in the genome.

Page 5 of 13
 Mechanism
Genes are small segments of DNA that instruct your cells to make
certain proteins when specific conditions are met.

Mutated genes, on the other hand, may cause your cells to make
too much or too little of the necessary protein. Even small changes
can have a domino effect across your body — just as tiny changes in
computer code can affect an entire program.

Gene therapy can address this issue by:

• replacing a missing or “broken” gene with a working copy

• turning off malfunctioning genes

• adding genes to immune cells to help them better target

diseased cells

Viral vectors

Scientists don’t have tweezers small enough to edit DNA by hand.

Instead, they recruit a surprising ally to work on their
behalf: viruses

Typically, a virus would enter your cells and alter your DNA to
create more copies of itself. But scientists can switch out this
programming with their own, hijacking the virus to heal instead of
harm. These vectors, as they’re called, don’t have the parts they

Page 6 of 13
need to cause disease, so they can’t make you sick the way a
regular virus could.

Figure 4: Viral and Non-viral Vector System

Nonviral vectors
In this system, genetic material is extracted from the target tissue
or bone marrow, then cultivated and manipulated in vitro before
being introduced back into the target tissue through transduction
or transfection. This method avoids immunologic issues, but it is
primarily used in cases where the target cells serve as sources for
protein secretion, such as in the treatment of ADA or hemophilia,
or as a cancer vaccine. Consequently, there are significant

Page 7 of 13
limitations to the use of ex vivo delivery. Additionally, currently,
only a small percentage of the reimplanted cells remain viable.

Types of gene therapy

There are two types of gene therapy:

Figure 5: In Vivo Delivery

1. In Vivo Delivery
In vivo delivery is defined as the transfer of genetic material
through the appropriate vector, either viral or nonviral, to the
target tissue. This could be the most powerful, but for now
this is the lowest level strategy. The problem of this way is that
when vectors are generated, they do not target to right tissue
sites in adequate quantity but developing the targeting
mechanism and development of vector can overcome this
issue.

Page 8 of 13
 2. Ex Vivo Delivery
In this system the genetic
material is explanted from
the target tissue or bone
marrow, cultivated and
manipulated in vitro, and
then transducted and/or
transfected into the target
tissue. There are no
immunologic problems in
this way but only the
technique is used in cases
where the target cells act as
Figure 6:Ex Vivo Delivery
protein secretion resources
(like the treatment of ADA or hemophilia) or as a vaccine for
cancer treatment, so there are major limitations on the use
of ex vivo delivery. In addition, at present only a small
percentage of reimplanted cells remain viable
Each type has its own benefits:

Benefits of in vivo Benefits of ex vivo

therapies therapies

can deliver vectors across the body, better at targeting

which is useful for bone or blood specific organs and cell
diseases types

tend to pose fewer

quicker and less invasive
safety risks

Page 9 of 13
Gene therapy is different from genetic engineering, which means
changing otherwise healthy DNA for the purpose of enhancing
specific traits. Hypothetically, genetic engineering could potentially
reduce a child’s risk of certain diseases or change the colour of
their eyes. But the practice remains highly controversial since it
hovers very close to eugenics.

Examples of Available Gene Therapies

CAR T-cell therapy:

So, CAR T-cell therapy is pretty neat. It's a superheroine power
given to the immune cells. They take your T cells, fix them in the lab
so they can recognize your cancer cells, and inject them back into
you.

Figure 7: CAR T-Cell Therapy

Page 10 of 13
 It has been a real game-changer, especially for some of these blood
cancers such as large B-cell lymphoma and acute lymphoblastic
leukemia, or ALL. There's that very famous one: Yescarta. It's saved
a lot of patients who didn't have many choices left.

Zolgensma: Gene Therapy for SMA

Spinal Muscular Atrophy is one of those hard ones, especially on

little kids. But there is this therapy-Zolgensma that's pretty much
making a big difference.

Figure 8: Zolgensma

They are, in a way, delivering healthy copy of the SMN1 gene to

kids' cells. It's like almost providing their body with instructions
they were lacking. It mainly targets under-2-year-olds and has
saved many families.

Luxturna:Gene Therapy for Vision Loss

Imagine that you may be able to correct a genetic defect that is

turning your sight away. That is what Luxturna does for patients

Page 11 of 13
with a condition called Leber congenital amaurosis (LCA).

Figure 9: Luxturna

It addresses mutations in the RPE65 gene. They inject it right into

the retina, and it heals it back up. It is not a cure, but it has been
huge help for most of these people.

Page 12 of 13
Bibliography
(2020, 9). Retrieved from American Academy of Pediatrics:
https://publications.aap.org/pediatrics/article/146/3/e20200729/36757/Gene-Therapy-for-
Spinal-Muscular-Atrophy-Safety?autologincheck=redirected
Administration, U. F. (n.d.). How Gene Therapy Can Cure or Treat Diseases. Retrieved from
https://www.fda.gov/consumers/consumer-updates/how-gene-therapy-can-cure-or-treat-
diseases
Administraton, U. F. (n.d.). How Gene Therapy Can Cure or Treat Diseases. Retrieved from
https://www.fda.gov/consumers/consumer-updates/how-gene-therapy-can-cure-or-treat-
diseases
Chauhan, D. T. (2019, 6 17). Gene Therapy: Types, Vectors [Viral and Non-Viral], Process, Applications
and Limitations. Retrieved from Genetic Education: https://geneticeducation.co.in/gene-
therapy-types-vectors-viral-and-non-viral-process-applications-and-limitations/
Darryl Leja, B. S. (2024, 11 9). Gene Therapy. Retrieved from National Human Genome Research
Institute: https://www.genome.gov/genetics-glossary/Gene-Therapy
FDA approves novel gene therapy. (2017, 12 18). Retrieved from FDA: https://www.fda.gov/news-
events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-
inherited-vision-loss
Gene therapy: principles, challenges and use in clinical practice. (2024, 5 7). Retrieved from Springer
Nature Link: https://link.springer.com/article/10.1007/s00508-024-02368-8
Jennifer N. Brudno, M., Marcela V. Maus, M. P., & Christian S. Hinrichs, M. (2024, 11 4). CAR T Cells
and T-Cell Therapies for Cancer. Retrieved from JAMA Network:
https://jamanetwork.com/journals/jama/article-abstract/2825799
Joseph W. Fischer, N. B. (2021, 6 18). CAR-T Cell Therapy: Mechanism, Management, and Mitigation
of Inflammatory Toxicities. Retrieved from Frontiers:
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.693016/full
Kay, M. (n.d.). Genetics and Genomics Program. Retrieved from Stanford Online:
https://online.stanford.edu/programs/genetics-and-genomics-program
Luxturna. (2019, 11 1). Retrieved from European Medicine Agency:
https://www.ema.europa.eu/en/medicines/human/EPAR/luxturna
Nouri, M. N. (2012, 7 6). Viral and nonviral delivery systems for gene delivery. Retrieved from
NAtional Library of Medicine: https://pmc.ncbi.nlm.nih.gov/articles/PMC3507026/
Sibylle Jablonka, L. H. (2022). Therapy development for spinal muscular atrophy. Retrieved from BMC:
https://neurolrespract.biomedcentral.com/articles/10.1186/s42466-021-00162-9
Swaim, E. (2023, 1 21). Your Guide to Gene Therapy: How It Works and What It Treats. Retrieved from
Healthline: https://www.healthline.com/health/how-does-gene-therapy-work
Vectors: Tools for Gene Delivery. (n.d.). Retrieved from Genehome builg by bluebird bio:
https://www.thegenehome.com/how-does-gene-therapy-work/vectors

Page 13 of 13