SCIENCE, TECHNOLOGY and SOCIETY

GENE THERAPY
LEARNING OBJECTIVES
After going through this module, you must be
able to:
1. Describe gene therapy and its various
forms;
2. Analyze an issue of gene editing employed
in gene therapy; and
3. Assess the problems, potential benefits,
and detriments to global health.

INTRODUCTION

Everyone desires treatment and cure of illnesses. The recent

advancement can now
address this concern through biotechnology application. The technology that
works on
manipulating the genome to correct defective genes to treat heritable diseases is
known as
Gene Therapy. Various disorders like Severe Combined Immunodeficiency
(SCID), Cancer,
Hemophilia, Diabetes, Cystic Fibrosis, Heart disease, and AIDS and even the
problems of
aging can be treated.

Gene Therapy allows the correction of disease-causing mutations to

prevent the onset
of diseases. It involves the process known as Gene Editing, which results in
modified genes.
In gene editing, the faulty genes are corrected or edited by inserting “good
genes.”
Although the technique is a breakthrough in the medical field, some
controversies occurred
in using this novel technology.

Learning this module will help you answer questions like What can gene
therapy do
to prevent such disease? Is gene therapy good or bad? Are there potential risks
involved?
How will this biotechnology affect society? This module will bring you to the
issues of gene
therapy, its various forms, and the societal impact of gene therapy. Hopefully,
this will
help you assess the benefits and potential risks that this technology would bring.

To get ideas about gene therapy, its success story, and the controversy of
gene editing,
watch the following videos:
Gene Therapy: Your Questions Answered
[Link]
 Gene Therapy for SMA Type 1: Evelyn’s Story
[Link]
 Why gene editing is so controversial. The World.
[Link]

From the video you’ve watched, it shows that gene therapy manipulates
genes to treat the patient’s disease. Thus, it is vital to understand the genes and
the human genome that express traits, including genetic disorders.
Genes and Human Genome

Genes are often called the blueprint of life that carry the information
responsible for the individual’s traits. These are the genetic materials in our
body cells, often called the DNA or Deoxyribonucleic Acid. The DNA or genes
contain the instruction that directs the cells in our body to make proteins.
Proteins do varied tasks in our cells. For example, it produces pigments, makes
muscles strong, and kills bacteria that invade our cells. Keratin protein, for
example, is produced by specific genes in the cells of our body line together to
form the skin and the fingernails ([Link]).

A genome is a complete set of DNA (Deoxyribonucleic Acid) or genes in a

cell or organism. It contains all the information needed by the cells in our body
to build, grow, and develop. A human genome consists of DNA packed together
in 46 chromosomes. These chromosomes are in homologous pairs. Each pair
contains a paternal chromosome (from the father)
and a maternal chromosome (from the mother). Thus, each human cells have 23
pairs of chromosomes. Twenty-two pairs are autosomes described as non-sex
chromosomes and a pair of sex chromosomes (X and Y chromosomes). These
chromosomal pairs dictate the organism’s characteristics.

A chromosome consists of 2 chromatids known as sister chromatids which

contain sequences of DNA or Deoxyribonucleic Acid. The nucleus of the cell
houses the DNA. The DNA is a double helix structure consisting of 2 strands.
Each DNA strand is composed of many genes made up of many chemical bases
such as Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). Changes in the
sequence of these chemical bases can result in genetic disorders.

The Genetic Disorders

Gene therapy applications have become helpful in the treatment of

genetic disorders. But the knowledge of why there are genetic disorders and how
they occurred will help you understand better the gene therapy applications.

You have learned that each of the human chromosomes contains genes or
DNA sequences. There are instances where these DNA sequences change.
Changes in the sequence of DNA will lead to the development of genetic
disorders. Correcting DNA sequences to treat genetic disorders is where gene
therapy application becomes useful.

Genetic disorders are diseases caused by a mutation or change in the

DNA sequence
of an individual. These mutations can either be due to an error in DNA
replication or environmental factors like diet and lifestyle that can trigger these
diseases. It can occur in
one gene, or there is an extra or missing chromosome. A change in a particular
portion of
our DNA affects the proteins that the genes code for, and the protein will fail to
carry its
normal function.

Classification of Genetic Disorders

There are three main categories of genetic disorders (Bautista et al.,

2018).

1. Single-Gene Disorders. Mutations in specific genes cause these. These

disorders are either a.) autosomal single-gene disorder and b.) X-linked disorder.
a.) The Autosomal single-gene disorder. It happens when the altered genes occur
in the 22 pairs of non-sex chromosomes. Examples are Huntington’s disease and
Cystic Fibrosis.

Huntington’s disease (HD)

It is a brain disease caused by a mutation in one gene called huntingtin.

Over time, this mutation causes damage to the brain. As a result, a person with
HD’s physical, mental, and emotional abilities will deteriorate, especially during
their prime working years ([Link]). In addition, family members inherit this
mutation from generation to generation

Cystic Fibrosis (CF)

It is a genetic disorder caused by a mutation in a gene called Cystic

Fibrosis Transmembrane Conductance Regulator (CFTR). This gene is essential
in controlling the flow of salts and fluids in the cells of our body. A person with
CF has a sticky mucus fluid build-up that blocks tubes and ducts in the body.
Over time, the mucus will build up in the
airways, making it difficult to breathe. The mucus will also trap bacteria that
lead to infections. It can also cause severe lung damage ([Link]).

b.) X-linked disorder. It refers to diseases in which the altered genes occur in the
sex chromosomes, specifically the X chromosomes. An example of an X-linked
condition is Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD)

It is a genetic disorder caused by a defective gene in the X chromosome.

This
gene is involved in the production of dystrophin, a protein essential for muscle
function and repair. A person with DMD lacks dystrophin and is characterized by
having progressive muscle weakness (everyday)

2. Chromosomal disorders. Those changes in the structure and number of

chromosomes.
The following are concepts that relate to chromosomal disorders.

 There is the excess or lacking chromosome, rearrangement of the
chromosome,
and contiguous gene-syndrome.
 Many structural abnormalities occur in the chromosome that is related to
cardiovascular disease leading to congenital heart disease.
 Abnormal breakage and reconstruction of the chromosomes result in the
chromosomal rearrangement.
 Structural rearrangement may lead to the loss or gain of genetic material.
 Losing genetic material is more harmful than gaining genetic materials.
 The gain of genetic materials leads to Down’s syndrome – has extra
chromosome
21 (Trisomy 21: Three copies of Chromosome 21 instead of two).

3. Multifactorial Inheritance. Changes in multiple genes combined with

environmental
and lifestyle factors such as diet or cigarette smoke caused multifactorial
inheritance
([Link]).
 There is a 5-10% possibility of multifactorial inheritance in the first-degree
relatives than second-degree relatives.
 Example: Cancer

Gene Therapy and How it Works

Bautista et al. (2018) described Gene Therapy as a method of treating or

preventing diseases by replacing, repairing, or turning on or off genes of a
patient’s cells. Gene therapy helps treat genetic disorders such as those
examples previously mentioned that occur due to mutations that alter or inhibit
protein functions. Gene therapy focuses on correcting defective genes by:

1. Randomly inserting a normal gene into the genome (the most common
technique).
2. Replacing the abnormal gene with the normal gene.
3. Repairing the abnormal gene.
4. Altering regulation of a particular gene.

The gene therapy method of treating conditions involves using vectors

(Viral Methods) or without vectors (Non-viral Methods) to move DNA or genes to
one cell. Conversely, vectors are vehicles or agents used to introduce or insert
genes into the cell. Some gene therapy vectors include retrovirus, adenovirus,
adeno-associated virus, cis and trans-acting elements, and herpes simplex virus.

In the non-viral method, the simplest way is the injection of naked DNA.
Employing
a non-viral method in gene therapy has a particular advantage over the viral
process because it can produce DNA on a large scale. Cells, tissues, and
organisms where gene therapy is employed are described as transgenic or
genetically modified.

Types of Gene Therapy

1. Somatic Gene Therapy

 It is not related to reproductive gene therapy.

 The genes are introduced to cells in the target organ (non-sex cells) to
produce
enzymes needed by the body to function well without altering the organism’s
genetic make-up.
 The changes caused are not transferred to the offspring.

2. Reproductive Gene Therapy or Germ-line Cell Therapy


 It involves introducing corrective genes to sex cells (sperm cells, egg cells)
or 4-day
old zygotes.
 The process removes the abnormalities that the offspring may inherit.

In gene therapy, the medical experts who did the procedure must
correctly identify
the genes responsible for the progression of the disease. Then, the modified gene
must
reach the cell or target organ accurately, controlled, and effectively. Medical
experts must
also note that cells can reject modified genes because of the body’s natural
defense
mechanism that causes most of gene therapy failures.
Benefits and Disadvantages of Gene Therapy

Benefits of Gene Therapy: `

1. It offers a cure for cancer, Parkinson’s disease, AIDS, asthma, diabetes, heart
diseases,
and other hereditary diseases.
2. It can replace defective cells.
3. It has promising potential in the field of medicine and other related areas like
agriculture.

Disadvantages of Gene Therapy:

1. Modifying organisms means modifying their capabilities.

2. Viral vectors could recover their ability to cause disease.
3. It can damage the gene pool resulting in multigene disorder.
4. High cost.
5. Ethical issues