Gene Therapy and Stem Cell Research

This assignment provides a comprehensive overview of gene therapy and stem cell research, featuring articles from reputable scientific journals such as Science, Nature Biotechnology, and The Lancet. It includes discussions on the use of CRISPR/Cas9 for genome editing in human hematopoietic stem cells, the development of gene therapies for diseases like sickle cell disease and hemophilia B, and the application of mesenchymal stem cell-based therapy for tissue regeneration. The assignment also covers the use of stem cells in regenerative medicine and their potential for treating various medical conditions.

STEM CELL AND GENE THERAPY

TABLE OF CONTENTS
INTRODUCTION...........................................................................................................................1
Problem statement.......................................................................................................................1
APPROACH AND METHODOLOGY..........................................................................................2
Literature Review........................................................................................................................2
SUMMARY.....................................................................................................................................5
REFERENCES................................................................................................................................1

INTRODUCTION
Genes are considered as the basic building blocks which are responsible for the concept
of inheritance in living beings. The presence of abnormalities in genes of individuals are due to
mutation in the sequence of DNA or gene structure which is known as genetic disorder. There
are various external and internal environmental factors which cause changes in genome such as
pollution, radiation exposure whereas internal can be inappropriate replication of DNA.
The mutation in genes or genetic disorders alters the protein structure formed by DNA.
As a result, the desired functionality of protein is affected which leads to abnormalities in
ordinary practicality of the body. These disorders may transfer from one generation to the other.
However, genetic disorders can be cured by replacing the mutation containing genetic sequence
with the functioning of stem cell with application of inherited techniques. The report will analyse
the scope and application of stem cells and gene therapy in treatment of genetic disorders.
Problem statement
Genetic disorders are not only cause due to physical abnormality but also influence the
psychological health and social wellbeing of the individual. These disorders are inherited in child
by birth from the parents. Thus, if an individual is diagnosed with it then there is great
probability that, the next generations of the family will have the same disorder. Along with the
physical stress, it also creates emotional burden. There is no specific treatment which can
completely cure genetically transferred disorders.
The selective treatment strategies which are available can only lower the influence of
intensity of symptoms. The treatment methods like bone marrow transplant are not suitable for
all individuals with disordered genes. Thus, the stem cell treatment and therapy can be
considered as the boom for curing these diseases. The concept has been rapidly transformed into
technology but is considered as the important part in research area. The analysis and research is
based on gene and stem cell therapy which is upcoming with important change in medical
science that will help number of individuals to recover from the severe impact of genetic
disorders.
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APPROACH AND METHODOLOGY
Literature Review
In the opinion of Sessa & et.al., (2016) most of the technologies which are present for
curing the genetic disorder can only improve the quality of life. They cannot eliminate the gene
mutation completely. The most effective treatment strategy developed so far in the field of
genetics is gene therapy. This theory is based on the concept that genetic disorders can be cured
by eliminating mutated gene by replacing it with another healthy gene. However, as per the
views of (De Ravin & et.al., 2016) this method is not convenient and simple for the health
professionals. They face the biggest challenge to deliver the healthy gene to the affected site or
cell, without giving rise to any new complexity. There are more than trillion cells in living
beings. Thus, it is very difficult to identify the defective cell which consist of mutation causing
element.
These challenges to the gene therapy are very critical to address. (Mandal & et.al., 2014)
believes that the healthy genes are inserted via viruses which acts as carriers. These viruses have
ability to identify mutated cells but they can be considered as external invaders by immune
system of patient. In order to deal with it, immune system can release antibiotics and their
interaction with these genetically modified carriers can result in organ failure and death of the
individuals. With the gene therapy there are also possibilities that these vector viruses can cause
viral and leads to diseases like cancer and transmission of disorders to reproductive cells.
According to (Liang & et.al., 2014) these drawbacks can be avoided by other alternatives of
treating genetic disorders. The most suitable mean of gene therapy is stem cell. Stem cells have
ability to distinguish between cells and have ability to generate same cellular structure by
division mechanism. Therapies like bone marrow transplantation, umbilical cord blood and using
the concepts of stem cell.
In stem cell therapies, the genetic disorders are cured by directly transferring the genes.
This approach is less complex as compare to the gene therapy. As per the views of (Trounson
and McDonald, 2015), genes can also be transferred directly by using liposomes to avoid the
complexity and drawbacks of genetically modified carriers. It suffers from disadvantage, that
this approach does not allow sophisticated controlled mechanism over therapeutic gene. Stem
cell therapy is based on the principle that self-healing abilities of the individuals can be used to
cure mutation of genes.
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In accordance to Schwartz & et.al., 2015 many genetic disorders appear in human body
due to changes in genes. These alterations affect organic structure severely and in most cases it
cannot be cured. Some familiar modification can also result in disease like cancer which can lay
never lasting impact on immune system of patient. Gene therapy is basically inheritance of
genetic components into the cells of service users, in order to treat the factors which has given
rise to specific disorder. This therapy increases level of protein in body which helps in fighting
against various diseases. However, stem cell medical aid is the process of inheriting live cell into
a human body in order to reduce the effect of disorders. In this procedure the cells may generate
or developed from service user or a donor. It can help in reducing problem related to genetic
disorder.
Gene therapy involves imparting of genetic material by the use of vector or carrier which
makes this process very complex. It also helps in transforming genes directly into patient’s body
without using any medicine or surgery. However, this procedure is not followed in stem cell
therapy. This procedure includes conversion of embryonic stem cells into adult type cell. Then
these cells are used for curing damaged body part or injury of patient. Study shows that
specialists use this therapy, especially for curing kids or children. These cells have the ability to
divide itself into specialised compartment which makes them better for curing various diseases.
But, these exchange of cells also involve several types of risks. Hence, this diagnosis is limited
to individuals who are suffering from life threatening disorders or facing problems for which no
other therapies are available.
As per the views of Smith & et.al., 2014 genetic disorders are basically congenital
mistake of metabolism, which results in genial alterations that interrupts the creation of specific
enzymes. Diagnosis of such problems include change in diet plan or imparting of the particular
protein which is been missing from human body. Various strategies are implemented by health-
care professionals in order to cure these problems. These approaches vary according to
individuals needs and demand. Further, it is also based on type of disease from which patient is
suffering from. For example, a genetic condition related with heart imperfection may be cured
with surgery like heart transplantation. However, in opinion of Lane, Williams & Watt, 2014
there are various situations where service users are suffering from sickle cell disease which can
be cured by bone marrow transplants. Apparently, some gene changes are related to risk of
developing cancer, where nurses may use various surgery methods to remove viruses that can
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develop into several harmful diseases. Genetic disorders can also affect a pregnant woman, in
most cases as it leads to miscarriage, and often results in death of new born. These diseases make
the body of patient extremely weak and also make their immune system ineffective to work.
Service users suffering from these disorders are often seen with symptoms like, depression, guilt
and shame. Strategies for curing genetic diseases include therapies like stem and gene.
In accordance to Nathwani & et.al., 2014 stem cell therapy is effective for treating
diseases such as hemoglobinopatheis, sickle cell anaemia, immunodeficiency diseases like fabry,
gaucher and Krabble. Other disorders which can be treated are osteoarthritis, fanconi anaemia
and diamond black fan syndrome. However, gene therapy is mostly used for treating diseases
like HIV aids, cancer, cystic fibrosis, and cardiovascular health concerns. Potential risks
involved in all these medical aid or therapies are only given to those patients or individual who
are seriously ill or not well.
As per the view of Findlay & et.al., 2014 there are two type of gene therapy which are
imparted to severely impaired adults. Somatic gene therapy includes process of imparting gene
into targeted cells in order to treat the service user. But there may arise a situation that in-spite of
treating patient’s genetic disorders chances might occur that they are being implemented to their
children. Germaline therapy includes modification of genes into egg or cells that helps in passing
genial moderations to future generation. It helps in preventing inherited diseases and is little
complex due to ethical and technical issues. In contrast, stem cell therapy includes adult eggs
which can be transformed into any type of young tissue and is mostly used in curing young
people.
In the opinion of Fares & et.al., 2014 there are various risks are related to these therapies.
Risk may include that the gene or stem cell therapy will provide the outcomes which are not as
effective as the health-care professionals expect it to be. It might happen that these therapies may
also worsen the disorder and make the situation more adverse. There might appear a chance that
the life of embryonic enzymes or survival of stem cells are too short and therefore they are
unable to fully heal or cure the diseases (Gene therapy using stem cell, 2017). Evenly high doses
of medicines given in these procedures are toxic for some patients and adversely impact their
immune system. Cell therapy also includes genuine risk such as, loss of control over stem eggs.
Lack of control over stem eggs holds the risk of converting into cancer. For getting over these
situation patients are recommended to ask frequent questions to health-care providers in relation
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to treatments given to them. They need to have critical understanding of the risks which would
help them in improving their condition.
In accordance to Sun & Zhao, 2014 many new innovations are made in gene therapy in
order to cure person suffering from diseases like HIV, cancer, etc. Research has shown that FDA
is seeking to encourage development of stem cell and gene therapy. For advancing in the field
the department has also released new policies and frame work for creating of enzymes or
embryos required for treating these chronic or acute disorders. Many new techniques like hybrid
methods are also being formulated in order to remove genetic disorder. These methods are
developed by combining two or more skills. For instance, Virosome are combined with liposome
to reduce effect of diseases like HIV.
As per the views of Genovese & et.al., 2014 many chemical methods are also being
developed by which women suffering from genetic disorders can also have healthy delivery.
Oligonucleotides is one of the technique used to improve condition of patient. This process
includes protection of DNA by health-care providers. It is protected from damage or must be
positively charged. These can also help in curing patient suffering from cancer where the
positively charged DNA reduces the effect of negative one. However, these new methods also
involve certain amount of risk like, there are more than trillion cells in living beings. Thus, it is
very difficult to identify the defective cell which consist of mutation causing element. Although
these methods have ability to identify cells but they can be considered as external invaders by
our immune system.
SUMMARY
This is to summarise the understanding about stem cell and gene therapy which are
effective for treating inherited disorder but can also result in risky health outcome. It shows that
hereditary diseases are not only causes by physical abnormality but also influence the
psychological health and social wellbeing of the individual's. These disorders are inherited in
child from their parents.
Further, study demonstrated that gene therapy is based on the concept that genetic disorders
can be cured by eliminating the mutated gene, by replacing it with another healthy gene. Study
also denoted that in gene therapy there are also possibilities that vector viruses can cause viral
and leads to diseases like cancer and transmission of disorders to reproductive cells. Hence, the
report outlined various type of new innovations and techniques which are adopted in to reduce
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impact of chronic diseases. Study also revealed new policies and framework which is developed
which is developed by FDA
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REFERENCES
Books and Journals
De Ravin, S. S. & et.al., (2016). Lentiviral hematopoietic stem cell gene therapy for X-linked
severe combined immunodeficiency. Science translational medicine. 8(335). 335ra57-
335ra57.
Fares, I. & et.al., (2014). Pyrimidoindole derivatives are agonists of human hematopoietic stem
cell self-renewal. Science.345(6203). 1509-1512.
Findlay, V. J. & et.al., (2014). Epithelial-to-mesenchymal transition and the cancer stem cell
phenotype: insights from cancer biology with therapeutic implications for colorectal
cancer. Cancer gene therapy.21(5). 181.
Genovese, P. & et.al., (2014). Targeted genome editing in human repopulating haematopoietic
stem cells. Nature.510(7504). 235.
Lane, S. W., Williams, D. A. & Watt, F. M. (2014). Modulating the stem cell niche for tissue
regeneration. Nature biotechnology.32(8). 795.
Liang, X. & et.al., (2014). Paracrine mechanisms of mesenchymal stem cell-based therapy:
current status and perspectives. Cell transplantation. 23(9).1045-1059.
Mandal, P. K. & et.al., (2014). Efficient ablation of genes in human hematopoietic stem and
effector cells using CRISPR/Cas9. Cell stem cell.15(5). 643-652.
Nathwani, A. C. & et.al., (2014). Long-term safety and efficacy of factor IX gene therapy in
hemophilia B. New England Journal of Medicine.371(21). 1994-2004.
Ribeil, J. A. & et.al., (2017). Gene therapy in a patient with sickle cell disease. New England
Journal of Medicine.376(9). 848-855.
Schwartz, S. D. & et.al., (2015). Human embryonic stem cell-derived retinal pigment epithelium
in patients with age-related macular degeneration and Stargardt's macular dystrophy:
follow-up of two open-label phase 1/2 studies. The Lancet. 385(9967). 509-516.
Sessa, M. & et.al., (2016). Lentiviral haemopoietic stem-cell gene therapy in early-onset
metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label,
phase 1/2 trial. The Lancet.388(10043). 476-487.
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Smith, C. & et.al., (2014). Whole-genome sequencing analysis reveals high specificity of
CRISPR/Cas9 and TALEN-based genome editing in human iPSCs. Cell stem cell.15(1).
12-13.
Sun, N. & Zhao, H. (2014). Seamless correction of the sickle cell disease mutation of the HBB
gene in human induced pluripotent stem cells using TALENs. Biotechnology and
bioengineering.111(5).1048-1053.
Trounson, A. & McDonald, C. (2015). Stem cell therapies in clinical trials: progress and
challenges. Cell stem cell.17(1).11-22.
Online
Gene therapy using stem cell. (2017). [ONLINE]. Available through:
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382729/>
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