Applications of Biotechnology in Medical Science: Gene Therapy

By

Syeda Fariha Ahsan

21236052

syeda.fariha.ahsan@g.bracu.ac.bd

Section 2

Submitted for

BTE 101

Introduction to Biotechnology and Genetic Engineering

BRAC University

Spring Semester 2022

Assignment 1

Mini Report

Date: 09.02.2022
Introduction

In today’s world, it is not the infectious diseases that pose a threat to human lives but rather the chronic
diseases that present bigger challenges for medical scientists to overcome. Biotechnological research in
medicine provides solutions for incurable diseases such as Alzheimer’s disease, Parkinson’s disease, ALS,
cancer, and many more. Medical biotechnology uses living cells or molecules derived from living matter
for the research and development of medicines and healthcare, with the goal of improving human lives.
There are numerous prospective technological growth avenues in medical biotechnology with its
plethora of applications such as tissue engineering products, recombinant pharmaceuticals, stem cell
therapy, and gene therapy [1].

Fig. 1: Some applications of medical biotechnology.

I have chosen gene therapy because this technique not only helps to fight illnesses in the human body
but also develops cures for genetic disorders. Gene therapy may be described as the transfer of
modified genetic material into human cells, usually via viral transduction, to treat a disorder or disease
[2]. A gene is delivered into a cell through a genetically engineered carrier called a vector and viruses are
often used for this purpose. The nascent science of gene therapy offers significant medical progress
toward the solution of a wide range of human ailments, therefore the concept of using genetic
information collected from the human genome for disease treatment is very intriguing.

Fig. 2: A diagram showing how viruses (such as adenovirus) can be utilized to transmit recombinant
genetic material to neurons or other nervous system cell types. The steps include viral attachment to
the cell membrane, endosomal packaging and breakdown, vector distribution and integration into host
DNA, and protein expression [4].

Current research and usage

 Gene therapy is being used for the treatment of numerous genetic disorders by employing a
viral/non-viral vector for delivering the desired transgene. Clinical trials have been conducted
for gene therapy via Adeno-associated virus (AAV) based vectors with vector doses for ocular
diseases, muscular dystrophy, Parkinson’s disease, cardiac failure, hemophilia, and lipoprotein
lipase deficiency, with successful outcomes [6].
 Therapies for cardiac arrhythmias are being developed using codon-optimized engineered
bacterial voltage-gated sodium channel (BacNav) to improve the electrical excitability and
conduction of action potential in the heart. This treatment with BacNav significantly reduces the
effect of genetic mutations that diminish sodium current in mammalian voltage-gated sodium
channels that can create decreased tissue excitability, which can lead to a variety of neuronal,
skeletal muscle, and cardiac problems [5].
 Another use of gene therapy is based on the treatment of growth hormone-resistant dwarfism
in mice using a viral vector with a liver-specific transcriptional regulatory sequence to increase
insulin-like-growth factor 1 (IGF1) [3] in mice, which leads to a significant increase in body
weight and length [8].
 Fig.3: A schematic diagram of VGSC subunits [3].

Interest in this application

Gene therapy is a rapidly evolving field of biotechnology with new applications being developed every
day and thus, piquing the interest of various organizations.

 Spark therapeutics developed a gene-replacement therapy to treat a rare blindness-inducing

eye disorder in 2018, which was approved by FDA and estimated to generate $ 27 million in
revenue [7].
 Also, companies like uniQure are developing therapies to treat hemophilia B, Huntingdon’s
disease, and Parkinson’s disease [9].
 Furthermore, Crispr Therapeutics, Vertex, and BLUE are designing and conducting clinical trials
for treating sickle cell anemia [10].

Discoveries of this application

 According to a research of investigational gene therapy for sickle cell disease conducted by the
New York-Presbyterian/Columbia University Irving Medical Center discovered that a single dose
of this therapy returned blood cells to their natural shape and eradicated the disease's most
dangerous consequence for at least three years. LentiGlobin, the new gene therapy, employs
stem cells that are modified with a beta-globin gene that are obtained from the patient's body
and delivers it via lentiviruses [14].
 A study led by Aayushi Manchanda and a team of researchers at the Oregon State University
discovered a new method for rectifying the mutation in the otoferlin gene that causes
congenital hearing loss, a discovery which has facilitated the development of a gene therapy
that could possibly eradicate this disorder [11].
Fig.4: A diagram representing the difference between a normal red blood cell and a sickle red blood cell;
and the formation of sickle cell anemia.

Advantages

 The main advantage of gene therapy is to provide a patient afflicted with a genetic disorder, or a
terminal illness a chance to live a normal life.
 Gene therapy can eradicate or prevent genetic diseases by replacing a non-functional gene with
a functional gene such as gene treatment for Duchenne's muscular dystrophy, or Sickle Cell
Anemia [13].
 Gene therapy can help cure heredity diseases like cystic fibrosis by removing the faulty gene
from the affected individual’s genome and thereby ensuring the safety of their future
generations [12].
 Gene therapy can also eliminate or delay the onset of HIV/AIDS by silencing the gene and
preventing the development of the disease [13].

Limitations

 Gene therapy is an expensive procedure and therefore it is unaffordable to the common man
[12].
 One limitation of this technology is the lack of longevity of therapeutic transgene expression,
due to which patients may need to undergo frequent therapies [15, 13]. It also carries the risk of
the disease returning post-therapy.
 Another concern regarding gene therapy is that some viral vectors are inefficient at transferring
genetic material in the human cell [15], and the use of viruses as vectors has the potential risk of
infection by the viral vector [13].
 The current techniques of gene therapy lack the possibility of viral specificity, meaning that the
vector cannot be delivered into any specific cell and instead infect random cells in the
surrounding area of delivery [15].
 An important issue with gene therapy is controlling gene expression, which is the ability to turn
a particular gene “on” or “off” depending on the requirement of the treatment. The inability to
do so can lead to undesirable effects, but unfortunately, it is difficult to control gene expression
in such a manner [15].
  Lastly, there are ethical issues associated with gene therapy such as it can be used for
modifications in the human genome and these techniques could be misused by some people;
furthermore, a defective gene carried by an unborn child can be revealed through prenatal
testing which may lead to abortion and thus creating ethical problems [12, 13].

Future Prospects

Fig.5: A schematic representation of RNA interference.

 A new procedure for gene transfer is post-transcriptional gene silencing, or RNA interference,
which is used for selective and persistent gene suppression and can help treat numerous
incurable diseases such as HIV/AIDS. In this procedure, specific gene expression is silenced by
RNA interference through the production of a short homologous RNA sequence from a viral
vector that forms a hairpin which is used to switch off a gene [15].
 Another promising technique of gene therapy is exon skipping, which is assumed to have
therapeutic capabilities for patients suffering from DMD (Duchenne’s muscular dystrophy) and
increase their life expectancy by lowering the condition's morbidity. Exon skipping basically
works through the production of a short RNA fragment that binds to a splice site that hinders
normal posttranslational modification, resulting in a protein with one less exon [15].

Conclusion

Gene therapy has developed, and continues to develop, solutions to the previously incurable diseases in
the human body. Due to gene therapy, many patients have been successfully treated and are able to live
a normal, happy, and healthy life. Despite of the limitations of this technique with the delivery
mechanism and ethical issues associated with it, the advantages of gene therapy far outweigh the
disadvantages. Gene therapy is an exciting new approach and with more genes and their functions being
discovered every day by scientists, the potential of this treatment is limitless and will transform the field
of medicine for the betterment of human life.
References

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