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A SEMINAR REPORT ON THE USE OF

VIRUSES AS GENE VECTORS


BY
MOSES TOLORUNLEKE OLALEMI
20/57MB/01458

SUPERVISOR- DR. W. T. ABORISHADE


OUTLINE

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Vectors

31.3%

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Viral Vectors

• Viral vectors are genetically engineered viruses carrying modified viral DNA or RNA

that has been rendered noninfectious, but still contain viral promoters and also the

transgene, thus allowing for translation of the transgene through a viral promoter

(Nurliyana et al., 2020).

• However, because viral vectors frequently are lacking infectious sequences, they require

helper viruses or packaging lines for large-scale transfection (Nurliyana et al., 2020).

• Viral vectors are tools commonly used by molecular biologists to deliver genetic

material into cells ((Nurliyana et al., 2020).

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Characteristics of Viral Vectors

• Safety: Viral vectors are modified in such a way as to minimize the risk of handling

them which involves the deletion of a part of the viral genome critical for viral

replication (Demirer et al., 2019).

• Low toxicity: The viral vector should have a minimal effect on the physiology of the

cell it infects.

• Stability: Some viruses are genetically unstable and can rapidly rearrange their

genomes. This is detrimental to predictability and reproducibility of the work conducted

using a viral vector and is avoided in their design (Demirer et al., 2019).
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Characteristics of Viral Vectors

• Cell type specificity: Most viral vectors are engineered to infect as wide a range of cell

types as possible. However, sometimes the opposite is preferred. The viral vector can be

modified to target the virus to a specific kind of cell. Viruses modified in this manner

are said to be pseudotyped (Wulff, 2023).

• Identification: Viral vectors are often given certain genes that help identify which cells

took up the viral genes. These genes are called markers. A common marker is resistance

to a certain antibiotic. The cells can then be isolated easily, as those that have not taken

up the viral vector genes do not have antibiotic resistance, and so cannot grow in a

culture with the relevant antibiotic present (Wulff, 2023).


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Types of Viral Vectors

1. Retrovirus

• Retroviruses are one of the mainstays of current gene therapy approaches. The
recombinant retroviruses such as the Moloney murine leukemia virus have the ability to
integrate into the host genome in a stable fashion.

• They contain a reverse transcriptase to make a DNA copy of the RNA genome, and an
integrase that allows integration into the host genome.

• They have been used in a number of FDA-approved clinical trials such as the X-
linked severe combined immunodeficiency (SCID-X1 trial) (Cavazzana-Calvo et al.,
2020).

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Types of Viral Vectors

2. Lentivirus

• Lentiviruses are a subclass of retroviruses. They are sometimes used as vectors for gene
therapy thanks to their ability to integrate into the genome of non-dividing cells, which
is a unique feature of lentiviruses, as other retroviruses can infect only dividing cells.

• The viral genome in the form of RNA is reverse-transcribed when the virus enters the
cell to produce DNA, which is then inserted into the genome at a random position by
the viral integrase enzyme (Marini et al., 2020)

• Clinical trials that utilized lentiviral vectors to deliver gene therapy for the treatment of
HIV experienced no increase in mutagenic or oncologic events (Montin et al., 2019).

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Types of Viral Vectors

3. Adenovirus

• As opposed to lentiviruses, adenoviral DNA does not integrate into the genome and is
not replicated during cell division (Bulcha et al., 2021). This limits their use in basic
research, although adenoviral vectors are still used in in vitro and also in vivo
experiments (Bulcha et al., 2021).

• Scientists are currently investigating adenoviruses that infect different species to which
humans do not have immunity, for example, the chimpanzee adenovirus used as a vector
to transport SARS-CoV-2 spike gene in Oxford AstraZeneca COVID vaccine.
PEGylation of adenoviruses for gene therapy can help prevent adverse reactions due to
pre-existing adenovirus immunity (Bulcha et al., 2021).

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Application of Viral Vectors

1. Basic Research

• Viral vectors were originally developed as an alternative to transfection of naked DNA

for molecular genetics experiments. Compared to traditional methods of transfection

(like calcium phosphate precipitation): transduction can ensure that nearly 100% of

cells are infected without severely affecting cell viability (Vakilian et al., 2020).

• Furthermore, some viruses integrate into the cell genome facilitating stable expression

(Vakilian et al., 2020).

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Application of Viral Vectors

2. Vaccines

• A live vector vaccine is a vaccine that uses an organism (typically virus or bacterium)
that does not cause disease to transport the pathogen genes into the body in order to
stimulate an immune response (Dai et al., 2019).

• The genes used in such vaccines are usually antigen coding surface proteins from the
pathogenic organism. They are then inserted into the genome of a non-pathogenic
organism, where they are expressed on the organism's surface and can elicit an immune
response (Dai et al., 2019).

• Unlike attenuated vaccines, viral vector vaccines lack other pathogen genes required for
replication, so infection by the pathogen is impossible. Adenoviruses are being actively
developed as vaccine vectors (Yadav et al., 2020).

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Application of Viral Vectors

3. Viral Vectors for Cancer Gene Therapy

• An alternative approach to cancer gene therapy has been to harness the inherent ability

of viruses to replicate and lyse cells.

• Approaches to achieve safe tumour-specific replication have generally involved the

deletion of viral genes that are necessary for replication in normal cells, which creates a

mutant virus that can only replicate in tumour cells in which the missing function is

supplied (Mantwill et al., 2021).


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CONCLUSION
• The utilization of viruses as gene vectors represents a revolutionary approach to addressing genetic diseases,

cancer, infectious diseases, and more. This technology has already yielded significant breakthroughs, from

approved gene therapies for rare disorders to the rapid development of vaccines against emerging infectious

diseases like COVID-19.

• However, it is essential to approach this field with caution, as safety concerns, immune responses, and ethical

considerations must be addressed diligently. As research progresses, the potential for personalized medicine

and innovative therapies continues to grow, offering hope for improved health and well-being in the future.

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RECOMMENDATION
• Encourage ongoing research in viral gene vectors, focusing on the development of safer

and more efficient vectors. Explore novel viral vectors and advanced delivery methods

to expand the range of treatable diseases.

• Prioritize safety in the development and clinical application of viral vectors. Rigorously

assess potential risks and conduct comprehensive preclinical testing to ensure patient

safety. Maintain ethical standards and comply with regulatory guidelines.

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REFERENCES
• Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. and Gao, G. (2021). Viral vector platforms within the gene therapy landscape. Signal transduction and targeted
therapy, 6(1): 53-55.

• Cavazzana-Calvo, M., Hacein-Bey, S., Basile, G. D. S., Gross, F., Yvon, E., Nusbaum, P. and Fischer, A. (2020). Gene therapy of human severe combined
immunodeficiency (SCID)-X1 disease. Science, 288(5466): 669-672.

• Dai, X., Xiong, Y., Li, N. and Jian, C. (2019). Vaccine types. In Vaccines-the history and future. IntechOpen. 3:1-19

• Demirer, G. S., Zhang, H., Matos, J. L., Goh, N. S., Cunningham, F. J., Sung, Y. and Landry, M. P. (2019). High aspect ratio nanomaterials enable delivery of
functional genetic material without DNA integration in mature plants. Nature nanotechnology, 14(5): 456-464.

• Javed, M., Nadeem, A. and Hassan, F. U. (2021). Introduction to Molecular Genomics. Bentham Science Publishers. 12:1-10

• Mantwill, K., Klein, F. G., Wang, D., Hindupur, S. V., Ehrenfeld, M., Holm, P. S. and Nawroth, R. (2021). Concepts in oncolytic adenovirus
therapy. International Journal of Molecular Sciences, 22(19): 105-122.

• Marini, B., Kertesz-Farkas, A., Ali, H., Lucic, B., Lisek, K., Manganaro, L. and Lusic, M. (2020). Nuclear architecture dictates HIV-1 integration site
selection. Nature, 521(7551): 227-231.

• Montini, E., Cesana, D., Schmidt, M., Sanvito, F., Ponzoni, M., Bartholomae, C. and Naldini, L. (2019). Hematopoietic stem cell gene transfer in a tumor-
prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nature biotechnology, 24(6): 687-696.

• Nurliyana Mohd, Y., Natasha Nur Afiqah, M. N. F., Mohd Azuraidi, O., Mohd Azmi, M. L. and Nik Mohd Afizan Nik, A. R. (2020). Viruses, the vehicle for
cancer gene therapy: A Review. 3(1):1-15

• Ramadass, P. (2019). Cloning. MJP Publisher. 14:317-325

• Vakilian, H., Rojas, E. A., Rezaei, L. H. and Behmanesh, M. (2020). Fabrication and optimization of linear pei-modified crystal nanocellulose as an efficient
non-viral vector for in-vitro gene delivery. Reports of Biochemistry & Molecular Biology, 9(3): 297-300.

• Wulff, E. (2023). Establishing Transductional Relationships: Viral Vectors as an Experimental Tool in ALS (Amyotrophic Lateral Sclerosis). Uttar Pradesh
Journal of Zoology, 44(1): 22-36.

• Yadav, D. K., Yadav, N. and Khurana, S. M. P. (2020). Vaccines: present status and applications. In Animal biotechnology 3:523-542). Academic Press.

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THANK YOU

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