GENETHERAPY
Objectives
• Introduction
• Principles of Gene Therapy
• Types of gene therapy
• Vectors for gene therapy
• Methods of gene therapy
• applications Gene therapy
• Conclusions
• References
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Introduction
• Gene therapy has the potential to treat diseases that cannot be treated
with conventional medicine. It is applied by transferring one or more
nucleic acids into a patient’s cells or by modifying a defective gene.
The main factors of investment in gene therapy for human diseases
include the development of gene therapy vectors, optimization of
gene delivery under in vivo and in vitro conditions, and enhancement
of the clinical experience. Gene therapy, as an advanced technology,
goes beyond the modification of genetic disorders and has spread to
a wide range of applications (Azam et al., 2018).
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Introduction
• In fact, promising progress made in the treatment of leukemia using
modified chimeric antigen receptors (CAR) of T-cells encouraged
Science magazine to select cancer immunotherapy as the most
important scientific achievement of 2013. Effective approaches to
clinical gene therapy include gene delivery to non-dividing cells and
tissues (post-mitotic cells) in vivo, or gene delivery to autologous
cells out of the body (ex vivo) in which the gene is transferred to the
patient through adoptive transfer. Among viral vectors, the adeno-
associated viruses (AAVs) have shown the highest clinical success
in in vivo gene transfer (Azam et al., 2018).
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Principles of Gene Therapy
• 1) Gene modification :
• Replacement treatment: Replacing a natural gene with a non-natural
gene through homologous recombination.
• Modifier gene therapy: Restoring natural function to a defective gene
through selective reverse mutation.
• 2) Gene transfer method there are 3 physical, chemical, and biological
methods for gene transfer.
• 3) Gene transfer to specific cell line this line is somatic gene therapy
and sex cell gene therapy (Patil et al., 2012).
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Types of gene therapy
1) Somatic Gene Therapy :
In somatic gene therapy, the somatic cells of a patient are targeted for
foreign gene transfer. In this case the effects caused by the foreign
gene is restricted to the individual patient only, and not inherited by the
patient's offspring or later generations (Haurigot et al., 2013)
2) Germ Line Gene :
Therapy here, the functional genes, which are to be integrated into the
genomes, are inserted in the germ cells, i.e., sperm or eggs. Targeting of
germ cells makes the therapy heritable (Wolf et al., 2019).
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Vectors for gene therapy
• Viral vectors Retroviruses, adenoviruses and adeno-associated
viruses (AAV) some commonly used viral vectors whereas some less
commonly used viral vectors are derived from the Herpes simplex
virus (HSV-1) (Asad et al., 2017).
• Non- viral vectors It involves chemical and physical methods such
as direct injection of naked plasmid DNA (particle bombardment),
receptor-mediated endocytosis and gene transfer through liposomes,
polymers, nano particles etc (Foldvari et al., 2016).
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Adenovirus as a vector in gene
therapy
Asad et al., 2017
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Methods of gene therapy
• There are mainly two approaches for the transfer of genes in gene
therapy:
• 1. Transfer of genes into patient cells outside the body (ex vivo gene
therapy).
• 2. Transfer of genes directly to cells inside the body (in vivo) like
brain cells (Cynthia et al., 2018).
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Cynthia et al., 2018
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Gene therapy applications
• 1-Cancer include glioblastoma, breast cancer, head and
neck cancer, non-small cell lung cancer and prostate cancer.
• 2-Neurological disorders include Parkinson’s
disease, Alzheimer’s disease.
• 3-Inherited diseases include Haemophilia, Cystic
fibrosis, “Severe combined immunodeficiencies” (SCID).
• 4-Infectious diseases tuberculosis, malaria, HIV and influenza.
• 5-Cardiac disease (Ginn et al., 2013).
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Conclusions
• Gene therapy has made a number of achievements in the last decade.
Several significant successes such as treatments now available for
diseases such as cystic fibrosis, diabetes, Alzheimer’s disease,
Parkinson’s disease, various cancers, etc, can be mentioned. In other
words, gene therapy can be applied to a wide range of diseases and
includes many methods of gene transfer. Other vector systems are
expected to provide further advancement in their clinical
applications. Next-generation protocols that will help expand the
range of diseases treatable by gene therapy are currently being
developed.
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References
1- Yazdani, Azam, et al. "Gene therapy: a new approach in modern
medicine." International Journal of Medical Reviews 5.3 (2018): 106-117.
2- Dunbar, Cynthia E., et al. "Gene therapy comes of age." Science 359.6372
(2018).
3- Patil, P. M., et al. "Review article on gene therapy." Research Journal
of Pharmacology and Pharmacodynamics 4.2 (2012): 77-83.
4- Ginn, Samantha L., et al. "Gene therapy clinical trials worldwide to 2012–an
update." The journal of gene medicine 15.2 (2013): 65-77.
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5- Asad, Antonela S., et al. "Viral gene therapy for breast cancer: progress
and challenges." Expert opinion on biological therapy 17.8 (2017): 945-959.
6- Foldvari, Marianna, et al. "Non-viral gene therapy: Gains and challenges
of non-invasive administration methods." Journal of Controlled Release 240
(2016): 165-190.
7- Wolf, Don P., Paul A. Mitalipov, and Shoukhrat M. Mitalipov. "Principles
of and strategies for germline gene therapy." Nature medicine 25.6 (2019):
890- 897.
8- Haurigot, Virginia, and Fatima Bosch. "Toward a gene therapy for
neurological and somatic MPSIIIA." Rare Diseases 1.1 (2013): 3254-
71.
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