Gene therapy is the therapeutic delivery of nucleic acid into a patient's cells as a drug to treat disease. The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I. Not all medical procedures that introduce alterations to a patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients. Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

1. ReviewReview On Gene TherapyOn Gene Therapy
--A New way in Biotechnology

2. Contents
• Introduction
• Literature Review
• Method of Gene Transfer
• Viruses as Vectors
• Gene Therapy Successes
• Gene Therapy Disappointments
• Regulation of Gene Therapy
• Advantages and Disadvantages of Gene Therapy
• Recent Developments
• Conclusion
• References

3. Introduction
• Gene therapy is a treatment or cure for disorders caused
by mutated genes.
• It involves adding a normally functioning copy of the gene(s)
to enough affected cells to restore normal function.

4. • Germline gene therapy would be the permanent transfer
of a gene into sperm or egg cells.
– Future generations would be “cured”.
• Somatic cell (body cell) gene therapy is ideally only the
transfer of genes to the affected cells.

5. Literature Review
The Best of Times, the Worst of Times.
W. French Anderson
Norris Cancer Center, Room 6316, University of Southern
California, Keck School of Medicine, 1441 Eastlake
Avenue, Los Angeles, CA 90033, USA
(2000) Science.
The recent tragic death of a young gene therapy patient
has marred the field of gene therapy research. Yet,
as Anderson explains in a Perspective, encouraging new
results from a study in which a severe immunodeficiency
disease is corrected in two infants by delivery of the
defective gene ( Cavazzana-Calvo et al.) have brought
cautious optimism back to the gene therapy field [1].

6. Viral vectors for gene therapy: the art of turning
infectious agents into vehicles of therapeutics.
Mark A. Kay, Joseph C Glorioso & Luigi Naldini
Departments of Pediatrics and Genetics, Stanford
University Stanford, California, USA
(2001) Nature Medicine.
Considered by some to be among the simpler forms of
life, viruses represent highly evolved natural vectors for
the transfer of foreign genetic information into cells. This
attribute has led to extensive attempts to engineer
recombinant viral vectors for the delivery of therapeutic
genes into diseased tissues. While substantial progress
has been made, and some clinical successes are over
the horizon, further vector refinement and/or development
is required before gene therapy will become standard
care for any individual disorder. [3].
Literature Review

7. Method of Gene Transfer
Viral Vector Carrying Healthy Gene
Cell with mutated
gene(s)
Vector inserts
healthy gene into
cell
New gene in the
cell along with
original genes

8. Gene Therapy
To design and carry out a gene therapy treatment,
a researcher must:
1. Identify the gene(s) responsible for the disorder.
2. Make copies of the normal gene.
3. Insert the copies into vectors.
4. “Infect” the affected cells with the vectors.
5. Activate the gene so that transcription and
translation take place.

9. Viruses as Vectors
• Replicate by inserting their DNA into a host cell
• Gene therapy can use this to insert genes that
encode for a desired protein to create the
desired trait
• Four different types
– Adenovirus
– Adeno-Associated Virus (AAV)
– Retrovirus
– Herpes Simplex Virus (HSV)

11. Gene Therapy Successes
• Although no gene therapies have
been approved by the FDA for sale,
some diseases have been
experimentally successful:
– Melanoma (skin cancer)
– Severe Combined Immunodeficiencies
– Hereditary Blindness
– Sickle Cell Anemia

12. Gene Therapy Disappointments
• In 1999 a boy died due to an
immune response to an
adenovirus gene therapy vector.
• Four children have developed
cancer due to a retrovirus gene
therapy vector

13. Regulation of Gene Therapy
• Regulations covering genetic modification are part of
general guidelines about human-involved biomedical
research.
• The Helsinki Declaration (Ethical Principles for Medical
Research Involving Human Subjects) was amended by
the World Medical Association's General Assembly in
2008. This document provides principles physicians and
researchers must consider when involving humans as
research subjects. The Statement on Gene Therapy
Research initiated by the Human Genome Organization
(HUGO) in 2001 provides a legal baseline for all
countries. HUGO’s document emphasizes human
freedom and adherence to human rights, and offers
recommendations for somatic gene therapy, including
the importance of recognizing public concerns about
such research [11].

14. Advantages
• Gene therapy has the potential to eliminate
and prevent hereditary diseases such as
cystic fibrosis, ADA- SCID etc.
• It is a possible cure for heart disease, AIDS
and cancer.
• It gives someone born with a genetic disease
a chance to life.
• It can be used to eradicate diseases from the
future generations.

15. Disadvantages
• Long lasting therapy is not achieved by gene
therapy; Due to rapid dividing of cells benefits
of gene therapy is short lived.
• Immune response to the transferred gene
stimulates a potential risk to gene therapy.
• Viruses used as vectors for gene transfer may
cause toxicity, immune responses, and
inflammatory reactions in the host.
• Disorders caused by defects in multiple genes
cannot be treated effectively using gene
therapy.

16. Recent Developments
1. In a new gene therapy method developed by
University of Florida in Jan 2012, researchers
found treatment for a common form of blindness
( X- linked retinitis pigmentosa ) that strikes both
youngsters and adults.
2. A gene therapy called NLX-P101 dramatically
reduces movement impairment in Parkinson's
patients, according to results of a Phase 2 study
published on March, 2011 in the journal Lancet
Neurology.

17. Conclusion
Gene therapy is the insertion of genes into an individual's
cells and tissues to treat a disease, and hereditary diseases
in which a defective mutant allele is replaced with a
functional one. Although the technology is still in its
infancy, it has been used with some success. Antisense
therapy is not strictly a form of gene therapy, but is a
genetically-mediated therapy and is often considered
together with other methods.
In most gene therapy studies, a "normal" gene is inserted
into the genome to replace an "abnormal," disease-causing
gene. A carrier called a vector must be used to deliver the
therapeutic gene to the patient's target cells. Currently, the
most common type of vectors are viruses that have been
genetically altered to carry normal human DNA.

18. References
1. Anderson WF, Gene therapy: the best of times, the
worst of times, Science; 288, 2000: 627-629.
2. Ying QL, Nichols J, Evans EP, Smith AG, Changing
potency by spontaneous fusion, Nature; 416, 2002:
545-548.
3. Kay MA, Glorioso JC, Naldini L, Viral vectors for gene
therapy: the art of turning infectious agents into
vehicles of therapeutics, Nature Medicine; 7, 2001: 33-
40.
4. Delecluse HJ, Pich D, Hilsendegen T, Baum C,
Hammerschmidt W, A first generation packaging cell
line for Epstein-Barr virus derived vectors, Proceedings
of the National Academy of Sciences; 96, 1999: 5188-
5193.
5. Mitani K, Kubo S, Adenovirus as an integrating vector,
Current Gene Therapy; 2, 2002: 135-144.