F A C T S H E E T

GENE THERAPY 27
Produced by the Centre for Genetics Education. Internet: http://www.genetics.edu.au

Important points
• Gene therapy is ‘the use of genes as medicine’ involving the transfer of a therapeutic or working copy of a gene into specific
cells of an individual in order to repair a faulty gene copy
• The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favourably
modify the clinical course of a condition
• Gene therapy is still an experimental discipline and much research remains to be done before this approach to the treatment
of condition will realise its full potential
– Gene therapy was used in 2000 by a French research group in the treatment of a form of immune deficiency due to a
mutation in a gene located on the X chromosome (Severe Combined Immune Deficiency). When two of the children
treated developed leukaemia in 2002 and 2003, caused when the virus used to deliver the therapeutic gene activated a
cancer-causing gene, the clinical trials were stopped but have now been resumed only for patients with no other treatment
options
• The challenge of developing successful gene therapy for any specific condition is considerable:
– The condition in question must be well understood
– The underlying faulty gene must be identified and a working copy of the gene involved must be available
– The specific cells in the body requiring treatment must be identified and accessible
– A means of efficiently delivering working copies of the gene to these cells must be available
• The problem of ‘gene delivery’ ie. how to get the new or replacement genes into the desired tissues, is very complex and
challenging. Some of the ‘vectors’ for the role of delivering the working copy of the gene to the target cells include using
harmless viruses and stem cells
• In gene therapy, only body (somatic) cells and not the egg or sperm cells (germ cells) are targeted for treatment. Somatic gene
therapy treats the individual and has no impact on future generations as changes to the somatic cells cannot be inherited
• The strong consensus view at present is that the risks of manipulation of the genes in the egg or sperm cells far exceed any
potential benefit and should not be attempted

What is gene therapy? A case study of gene therapy for a genetic condition
Gene therapy is ‘the use of genes as medicine’. It involves the Another form of immune deficiency is due to a mutation in a gene
transfer of a therapeutic or working gene copy into specific cells located on the X chromosome and is called Severe Combined
of an individual in order to repair a faulty gene copy. Thus it may Immune Deficiency (SCID). This ‘X-linked condition’ only
be used to replace a faulty gene, or to introduce a new gene whose affects boys (see Genetics Fact Sheet 10 for an explanation of the
function is to cure or to favourably modify the clinical course of a inheritance pattern of genes located on the X chromosome).
condition. The use of gene therapy in 2000 in the treatment of this
The scope of this new approach to the treatment of a condition condition by a French research group led by M. Cavazzana-Calvo
is broad, with potential in the treatment of many genetic conditions, was hailed as the first example of a genetic condition being
some forms of cancer and certain viral infections such as AIDS. successfully treated by gene therapy and is a milestone in medical
Gene therapy remains an experimental discipline however history.
and much research remains to be done before this approach to the • Seven out of ten infants treated to date have restored immune
treatment of certain conditions will realise its full potential. function. Two of the children treated by the gene therapy
The majority of clinical gene therapy trials are being however developed leukaemia in 2002 and 2003, caused when
conducted in the United States and Europe, with only a modest the virus used to deliver the therapeutic gene activated a
number initiated in other countries, including Australia. The cancer-causing gene (an oncogene – see Genetics Fact Sheet 47)
majority of these trials focus on treating acquired conditions such • The clinical trials were halted but have now been resumed
as cancer. The only gene therapy that has been approved for only for patients with no other treatment options
routine treatment so far is for a form of cancer which was approved • This experience illustrates the need for this therapy to be
in China in early 2004. conducted as part of clinical trials
A form of immune deficiency called adenosine deaminase
(ADA) deficiency was the first condition to be treated with a gene How is gene therapy carried out?
therapy approach in humans in the early 1990s. It is also the first
The challenge of developing successful gene therapy for any
condition for which therapeutic gene transfer into stem cells (see
specific condition is considerable. The condition in question must
later) has been attempted in the clinical arena (Candotti F, 2001).

www.genetics.edu.au The Australasian Genetics Resource Book – © 2007  1

 F A C T S H E E T
GENE THERAPY 27

be well understood and the underlying faulty gene identified. these cells are located in the testes and in females, in the ovaries.
A working copy of the gene involved must be available, the These special reproductive cells are called ‘germ cells’.
specific cells in the body requiring treatment must be identified All other cells in the body, irrespective of whether they are
and accessible and finally, a means of efficiently delivering working brain, lung, skin or bone cells, are known as ‘somatic cells’.
copies of the gene to these cells must be available. In gene therapy, only somatic cells are targeted for treatment.
Of all these challenges, the one that is most difficult is the Therefore any changes to the genes of an individual by gene
problem of ‘gene delivery’ ie. how to get the new or replacement therapy will only impact on the cells of their body and cannot be
genes into the desired tissues. Some of the ‘vectors’ for the role of passed on to their children. Changes to the somatic cells cannot be
delivering the working copy of the gene to the target cells include passed on to future generations (inherited).
using: Somatic gene therapy treats the individual and has no impact
on future generations.
a) Harmless viruses
One of the most promising methods currently being developed is An example of somatic gene therapy for an inherited condition
the use of harmless viruses that can be used to carry genes into Imagine, for example, a little boy with haemophilia, a condition
cells. that is caused by a faulty gene that makes his liver unable to make
Scientists now have the knowledge and skills to remove the blood clotting factor 8 (see Genetics Fact Sheet 40).
virus’ own genes and to replace them with working human genes. • Gene therapy would involve putting a working copy of the
These altered viruses can then be used to smuggle genes into cells gene which codes for factor 8 into his liver cells so that his
with great efficiency. When viruses are used in this way they are liver could then produce adequate levels of factor 8
known as vectors. • While the little boy himself would be cured, the altered genes
Some of these vectors are capable of not only carrying the gene in his germ cells would remain unchanged and he could still
into the cell but also of inserting the gene into the genetic make- pass the faulty gene on to future generations
up of the cell.
Once in the right location within the cell of an affected Concerns with gene therapy of the egg or sperm cells
person, the transplanted gene is ‘switched on’. The transplanted
The possible genetic manipulation of the egg or sperm cells (germ
gene can then issue the instructions necessary for the cell to make
cells) remains the subject of intense ethical and philosophical
the protein that was previously missing or altered.
discussion.
The strong consensus view at present is that the risks of
b) Stem cells
germline manipulation far exceed any potential benefit and should
Another technique with potential is the use of stem cells in not be attempted.
delivering gene therapy. Stem cells are immature cells that can
differentiate or develop into cells with different functions. Safety considerations
In this technique, stem cells are manipulated in the laboratory
No therapy, established or experimental, is without some
in order to make them accept new genes that can then change
associated risk and the potential benefits of new treatments must
their behaviour.
always be balanced against such risks. The experience with gene
For example, a gene might be inserted into a stem cell that
therapy for the immunodeficiency condition SCID as described
could make it better able to survive chemotherapy. This would
above illustrates the need for this therapy to be conducted as part
be of assistance to those patients who could benefit from further
of clinical trials.
chemotherapy following stem cell transplantation.
Safety will appropriately remain an important consideration as
the field of gene therapy evolves.
Ethical considerations
While the body has many billions of cells, only a very small Other Genetics Fact Sheets referred to in this Fact Sheet: 10, 40, 47
proportion of these cells are involved in reproduction, the process
by which our genes are handed on to future generations. In males

2  The Australasian Genetics Resource Book – © 2007 www.genetics.edu.au

 F A C T S H E E T
GENE THERAPY 27

Information in this Fact Sheet is sourced from:

Candotti F.(2001). Gene therapy for immunodeficiency. Current Allergy & Asthma Reports. 1(5):407-415.
Cavazzana-Calvo M et al.(2000). Gene therapy of human severe combined immunodeficiency (SCID-X1) disease. Science. 288(5466):669-672
The Gene Therapy Research Unit, The Children’s Hospital, Westmead, Australia [online]. Available from: http://www.chw.edu.au/prof/services/
genetherapy/ [Accessed June 2007]
U.S. Department of Energy Office of Science, Office of Biological and Environmental Research, Gene Therapy [online]. Available from: http://
www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml [Accessed June 2007]

Edit history
June 2007 (8th Ed)
Author/s: A/Prof Kristine Barlow-Stewart
Acknowledgements this edition: Gayathri Parasivam; Prof Ian Alexander
Previous editions: 2004, 2002, 2000, 1998, 1996, 1994, 1993
Acknowledgements previous editions: Mona Saleh; Bronwyn Butler; Prof Ian Alexander

www.genetics.edu.au The Australasian Genetics Resource Book – © 2007  3