Nucleic acid based therapeutic drug delivery system

NUCLEIC ACID BASED
THERAPEUTIC DELIVERY
SYSTEM
SUBMITTED BY:
T. SRI TEJA
M. PHARMACY
DEPARTMENT OF PHARMACEUTICS
5/19/2019 1Vignan Pharmacy college, Vadlamudi, Guntur

S.NO Table of contents Slide Number
1. Introduction 3
2. Gene Therapy 4
3. Types of gene Therapy 5
4. Germline Gene Therapy 6-7
5. Somatic cell Gene Therapy 8-13
6. Basic Process of Gene Therapy 14-24
7. Potential target diseases for gene
therapy
25-29
3. Limitations 30
4. Conclusion 31
5. References 32
Contents
5/19/2019
2
Vignan Pharmacy college, Vadlamudi, Guntur

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
disorders
• This technique has been a common research tool in the 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
• By the 1980s, a series of clinical trials demonstrated therapeutic efficacy from the
transplantation of virally transduced cell.
5/19/2019 3Vignan Pharmacy college, Vadlamudi, Guntur

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.
• Gene therapy quickly became an intensely investigated field with the promising
potential to devise treatment not only for genetic diseases but also for a wide range of
disorders including metabolic disorders, infectious diseases, chronic illnesses and
cancer.
• The power of gene therapy is derived from the ability to manipulate cell physiology at
genetic and epigenetic levels.
5/19/2019Vignan Pharmacy college, Vadlamudi, Guntur 4

Types of Gene Therapy
Gene Therapy
Germline Gene
Therapy
Somatic Gene
Therapy

Germ line Gene therapy
• In Germ line gene therapy(GGT) germ cells are modified by introduction of
therapeutic genes.
• Modifying a germ cell causes all the organism's cells to contain the modified
gene.
• The change is therefore heritable and passed on to later generations.
• For safety, ethical and technical reasons, it is not being attempted at present.

Figure : 1 Representing Germline Gene therapy

Somatic Cell Gene Therapy
• In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into
any cell other than a germ cell.
• Introduction of genes into bone marrow cells, blood cells, skin cells.
• It will not be inherited to later generations.
• Most focus on severe genetic disorders, including immuno deficiencies,
hemophilia, thalassaemia, and cystic fibrosis. such single gene disorders are good
candidates for somatic cell therapy.

Figure : 2 Representing Somatic cell Gene therapy

Types of Somatic Cell Gene Therapy
Ex Vivo
Can be applied to
only selected tissues
Cells are modified
outside the body and
transplanted back
In Vivo
The direct delivery of
the therapeutic gene
into the target cells
Cells are modified
inside the body and
transplanted back

Ex Vivo Gene Therapy

In Vivo Gene Therapy
• Direct delivery of therapeutic gene into target cell into patients body.
• Carried out by viral or non viral vector systems.
• It can be the only possible option in patients where individual cells cannot be
cultured in vitro in sufficient numbers (e.g. brain cells).
• In vivo gene transfer is necessary when cultured cells cannot be re-implanted in
patients effectively.

Figure : 3 Representing 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 function. 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.
• Delivery of gene into cells can also be accomplished by some other methods like
DNA complexes etc.

Gene Therapy
Viral Vector Non Viral Vector
Adenovirus vector
system for treating
common cold
Synthetic vector based
delivery for treatment of
cancer

VIRAL VECTOR
• Viruses have evolved a way of encapsulating and delivering their genes to human
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.

Figure : 4 Representing Virus Vector based Gene Therapy

TYPES OF VIRAL VECTORS
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

• 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 types of nucleic acids
1. Small DNA
2. Large DNA
3. RNA
NON VIRAL VECTOR

Methods of Non-viral Vector Gene Delivery
• Needle Injection
• Electroporation
• Gene Gun
• Hydroporotion
Physical Methods
(carrier free gene delivery)
• Inorganic Particles
• Synthetic/Natural biodegradable polymer
• Chitosan
• Dendrimers
Chemical Methods
Synthetic vector based
delivery

• Needle Injection: The genetic material of interest is administered through a
needle carrying syringe into tissue or systemic injection from a vessel. Without
any carrier it is the simplest and safest method of gene transfer. The efficiency is
low due to rapid degradation by nucleases in serum.
• Electroporation: The other terms used for electroporation are gene electro
injection, gene electro transfer. applying an electric field that is greater than the
membrane capacitance will cause charges of opposite polarity to line up on either
side of cell membrane thus forming a potential difference at a specific point on
the cell surface. As a result membrane breakdown form a pore and allows the
molecule to pass. Pore formation occurs in approximately 10 nanoseconds.
PHYSICAL METHODS

• GENE GUN: Employs a high pressure delivery system to shoot tissue with gold
or tungsten particles that are coated with DNA
• HYDROPORATION: It is also called as hydrodynamic gene transfer. The
technique uses hydrodynamic pressure to penetrate the cell membrane.
Hydrodynamic pressure is created by injecting large volume of DNA solution in
a fraction of time. This creates increased permeability of capillary endothelium
and forms pores in plasma membrane encircling parenchyma cells. The
therapeutic gene of interest can reach the cell through these pores and these
membrane pores are closed later thus keeping the genetic material inside the cell.
This technique is most commonly used for gene therapy research in hepatic cells.

CHEMICAL METHODS
Inorganic
particles
Polymer
basedLipid Based
•Ca. Phosphate
•Silica
•Gold
•Polyethyleneimine
• Chitosan
• Dendrimers
• Polymethacrylate
• Lipid nanoemulsions
• Solid lipid nano
particles
• Peptide

POTENTIAL TARGET DISEASES FOR GENE THERAPY

GENE THERAPY FOR TREATMENT OF GENETIC DISORDERS
• Genetic disorders are illnesses stemming from errors in a person’s genes
• Any mistake in a gene can alter how a specific protein is produced
• Without proper proteins, the body will not function properly and will take on a
chronic and possibly life threatening condition
• Genetic disorders can be congenital meaning they occur from birth or they may
develop over time

GENE THERAPY CURES BLINDNESS
• Cures blindness of inherited condition
• Inherited blindness caused by an abnormality in a gene called RPE65
• The condition appears at birth or in the first few months of life and causes
progressive worse and loss of vision.
• It can be treated by enabling access to cells beneath the retina of patients.

GENE THERAPY FOR CANCER TREATMENT
 ONCOGENE ACTIVATION:
- Done by using antisense therapy
- Reduces the expression of antigenic proteins responsible for malignancies
 VIRUS MEDIATED ONCOLYSIS:
- Adeno virus and herpes virus can infect and cause lysis of cancer cells.
 AUGMENTATION OF TUMOR SUPRESSOR GENE:
- It is done by repair of tumor suppressor gene in malignant cells.

GENE THERAPY IN SOME OTHER DISEASES
• GENE THERAPY CAN ALSO USED IN OTHER DISEASES LIKE
- Diabetes
- Cystic fibrosis
- Parkinson's Disease
- X-SCID (X- Linked severe combined immunodeficiency)
- Adenosine deaminase deficiency
- Muscular dystrophy

LIMITATIONS OF GENE THERAPY
• Immune hyper responsiveness directed against viral vector components may
leads to deactivation of gene
• Virus that used as vectors may also cause diseases inside the body.
• Once we does not have control over the site of insertion of genome

CONCLUSION
• 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.

REFERENCES
• S.P . Vyas and Khar; Controlled and targeted drug delivery system; 2nd edition;
Page. No: 520-560
• Charlie Yu Ming Hsu and Hasan Iludag; Nucleic Acid based gene therapeutics:
Delivery challenges and modular design of nonviral gene carriers and expression
cassettes to overcome intracellular barriers for sustained targeted expression;
Journal of Drug targeting; Page No-301-319; 2012; 20(4)
• https://en.wikipedia.org/w/index.php?title=Gene_therapy&oldid=886560975

Nucleic acid based therapeutic drug delivery system

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Ähnlich wie Nucleic acid based therapeutic drug delivery system

Ähnlich wie Nucleic acid based therapeutic drug delivery system (20)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

Nucleic acid based therapeutic drug delivery system