The document discusses the 'nucleic acid based therapeutic delivery system,' focusing on gene therapy's potential to treat various genetic and acquired diseases by introducing new genetic material into cells. It explains different gene therapy types, delivery methods using viral and non-viral vectors, and addresses challenges such as immune responses and insertion site control. The conclusion highlights the significant promise of gene therapy in treating numerous conditions, with ongoing advancements in the field and recent FDA approvals for multiple therapies.

1. “Nucleic Acid Based Therapeutic
Delivery System”
Assignment
Submitted to
NIMS INSTITUTE OF PHARMACY
MASTER OF PHARMACY
(2022-23)
Supervised By
Mr. Arsh Chanana
Associate Professor
Department of Pharmaceutics
Submitted By
Mr. Rahul Pal
Roll no. 2022MPHA029
M. Pharm (Pharmaceutics)
NIMS UNIVERSITY RAJASTHAN SHOBHA NAGAR,
JAIPUR, RAJASTHAN
INDIA, 303121
MAY, 2023
(BATCH: 2022-2023)

2. Nucleic Acid Based Therapeutic Delivery System
Rahul Pal, NIMS University Rajasthan, Jaipur Page|2
INTRODUCTION:
 The delivery of nucleic acid molecules into cells to alter physiological
functions at the genetic level is a powerful approach to treat a wide range of
inherited and acquired disorder.
 This technique has been a common research tool in laboratory for decades to
study gene functions.
 The therapeutic potential of this approach was not fully realized due to lack
of reliable and practical methods to transfer and express recombinant DNA in
mammalian cells.
Figure. 01 Representation of basic gene therapy
GENE THERAPY:
 Insertion of new genetic material into the cells of an individual with the
intention of producing a therapeutic benefit for the patient is human gene
therapy.
 The power of gene therapy is derived from the ability to manipulate cell
physiology at genetic and epigenetic levels.
 Gene therapies quickly an intensely investigated field with the promising
potential to devise treatment not only for genetic diseases.

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|3
The main two types of gene therapy as following:
Figure. 02 Type of different gene therapy
DIFFERENTIATION OF TYPES OF GENE THERAPY:

4. Nucleic Acid Based Therapeutic Delivery System
Rahul Pal, NIMS University Rajasthan, Jaipur Page|4
Figure: 03 Type of gene therapy
TYPES OF SOMATIC CELL GENE THERAPY:

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|5
DESCRIPTION ON EX-VIVO AND IN-VIVO:
Figure: 04 Representation of In-Vivo and Ex-Vivo gene therapy
BASIC PROCESS OF GENE THERAPY: Process of Gene Therapy
 A gene that is inserted directly into a cell usually does not functions, instead,
a carrier called a vector is genetically engineered to deliver the gene.
 Viruses are often used as vectors because they can deliver the new gene by
infecting the cell.

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|6
 Delivery of gene into cells can also be accomplished by some other method
like DNA complex's etc.
VIRAL VECTORS AND TYPES
Viruses have evolved a way of encapsulating and delivering their genes to huma cells in
a pathogenic way by manipulating the viral genome to remove disease causing gene and
inserting therapeutic one. Viruses bind to their hosts and introduce their genetic material
into the host cell. Viruses used are altered to make them safe, although some risks still
exist with this type of gene therapy.
1. Retrovirus vector system: Recombinant retrovirus have the ability to
integrate into the host genome in a stable fashion.
2. Adeno Virus vector system: Adeno virus with DNA genome is a good
carrier. Useful in treating common cold.
3. Adeno Associated virus vector: It is a single stranded, non-pathologic small
DNA Virus. It can integrate into Chromosome 19.
4. Herpes simplex virus vector: They persist into nervous cell. These viruses
have natural tendency to infect particular type of cell.

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NON-VIRAL VECTOR:
 The non-viral vectors are naked DNA, particle based and chemical based.
 They are administered by direct administration (plasmid DNA/naked DNA)/
chemical/physical.
 Most of cardiovascular clinical trials use non-viral vectors as a mode of gene
transfer.
 Non-viral vectors are generally used to transfer following type of nucleic
acids:
POTENTIAL TARGET DISEASES FOR GENE THERAPY (INHERITED DISORDER AND
CANCER):
GENE THERAPY FOR TRAETMENT OF GENETIC DIAORDER:
• Genetic disorder are illnesses steaming from errors in a person gene.
Small
DNA
Large
DNA
RNA

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|8
• Any mistake in gene can alter how a specific protein is produced.
• Without proper protein, the body will not function properly and will take on
a chronic and possibly life-threatening conditions.
• Genetic disorder can be congenital meaning they occur from birth or they may
develop over time.
GENE THERAPY FOR CANCER TREATMENT:
ONCOGENE ACTIVATION:
• Done by using antisense therapy
• Reduces the expression of antigenic protein responsible for malignancies.
VIRUS MEDIATED ONCOLYSIS:
• Adeno virus and herpes virus can infect and causes lysis of cancer cells.
AUGMENTATIONOF TUMOR SUPRESSOR GENE:
• It is done by repair of tumor suppressor gene in malignant cells.
GENE THERPAY IN SOME OTHER Diseases: The gene therapy can also use in
other disease like:
 Diabetes
 Cystic fibrosis
 Parkinson’s diseases
 X-SCID (X-linked combine immunodeficiency)
 Adenosine deaminase deficiency
 Muscular dystrophy

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|9
Figure: 06 Representation of gene therapy in different disorder
LIMINATIONS OF GENE THERAPY:
 Immune hyper responsiveness directed against viral vector components may
leads to deactivation of gene.
 Virus that used as vectors may also causes diseases inside the body.
 Once we do not have control over the site of insertion of genome.
CONCLSIONS:
 Nucleic acid based therapeutic delivery is a technique that will be very useful
for the treatment of many diseases.
 Gene therapy can be helpful in many genetic diseases which can prevent those
diseases for future generations.

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Rahul Pal, NIMS University Rajasthan, Jaipur Page|10
RECENT AND FUTURE ASPECTS:
1. The director of the centre for gene therapy at Nationwide Children's Hospital
talked about the challenges and opportunities of gene therapies for
neuromuscular diseases at the 2023 MDA conference.
2. New Castle, USA, May 25, 2023 (GLOBE NEWSWIRE) Growth Plus
Reports studied and calculated the size of the global market for gene therapy
in CNS disorders in 2022 and is expected to increase at a revenue CAGR of
29.3% during the forecast period 2023-2031.
3. The U.S. Food and Drug Administration (FDA) have voted that at their formal
meeting at the end of May, approval moves forward for a gene therapy for
Duchenne muscular dystrophy-a disabling genetic disease.
4. This year marks the first time multiple gene therapies for the same non-
oncology rare disease may be market authorized in the United States. They
include treatments for beta-thalassemia, haemophilia B, and potential
treatments for sickle cell disease.
5. U.S. Food and Drug Administration. “FDA Approves First Cell-Based Gene
Therapy to Treat Adult and Pediatric Patients with Beta-thalassemia Who
Require Regular Blood Transfusions.” 17 Aug 2022.
REFERENCES:
1) S.P. Vyas and Khar; “Controlled and target drug delivery system”, 2nd
edition; page no. 520-560.
2) Charlie Yu Ming Hsu and Hasan Iludag: “Nucleic Acid gene therapeutic:
Delivery challenges and molecular design of non-viral gene carriers and
expression cassettes to overcome intracellular barriers for sustained targeted
expression”; Journal of Drug Targeting: Page no. 301-319; 2012; 20 (4).