Recommendation Report to the National Institutes of Health
for Increased Support of Gene Therapy
Enoch Obeng
Table of Contents
Abstract...................................................................................................................... iii
Introduction................................................................................................................. 4
Findings....................................................................................................................... 5
Point 1: Use of Viral Vectors for
Gene Transfer................................................ 5
Virus Behavior Allows
for Effective Gene Transfer............................... 5
Adenovirus Vectors
Reduce Risk of Viral Infection.............................. 6
Point 2: Heavy Focus on Single Gene
Disorders............................................... 7
One Step at a Time……...................................................................... 7
Effects of Single Gene
Therapy............................................................ 7
Progress
with animals............................................................... 7
Progress
with animals............................................................... 8
Point 3: Venturing into Multigene
Therapy Treatments....................................... 9
Disclaimer/Ethical
Response…………......................................................................... 10
Conclusion………………………….. …................................................................... 11
References……………………………...................................................................... 12
iii
Abstract
In an attempt to
find better treatments for obscure ailments, scientist discovered that many
diseases can be traced to genes. Genes were then investigated and it became
clear that modifying certain genes can heal the diseases associated with those
genes. Although progress has been slow, there have been breakthroughs with use
of certain methods. It is now evident that viruses can be modified so that they
can store and transport normal genes to cells whose genes are defective. Gene
therapy, although in its early stages, has the potential to cure many diseases,
especially those that affect single genes. Because of such potential, gene
therapy should be supported as well as monitored to ensure safety and progress.
Introduction
The world of medicine is now
changing at an unprecedented pace and more needs to be done to ensure that
medicine keeps its lead over disease. This includes evolving medical practices
faster than diseases can adapt. In this day and age there are more
opportunities than ever through research and development to help the ailing.
One breakthrough method is the use of gene modification or transfer which is
commonly referred to as gene therapy. Gene therapy is the process of altering a
gene to portray a normal or favorable condition and then transferring the gene
to a subject whose gene for that condition may be defective. When done properly
gene therapy can better cure ailments with fewer treatments as opposed to
conventional medicines which may merely cover up the sickness while producing
unneeded side effects due to chemical imbalances. Because of this, more stock
should be put into gene modification procedures. This recommendation will
outline a systematic three point routine, with reviews from professionals in
the field, that showcase the most accepted method of gene modification and
their findings .By using an analysis of current and prospective protocols, one
can better understand how gene therapy works and why it could be so beneficial.
It should also be noted that preference with gene project funding should be
given in accordance with the research methods in this report because of the
amount of promise shown and higher chances of success.
Findings
The research gathered will be
presented in three points to show distinctions in the different phases of research.
Point 1: Use of Viral Vectors for Gene
Transfer
Findings have been gathered for
almost the last two decades which show that the best way to transfer genetic
information with hopes of widespread dispersion is by the use of viruses. This
is of course the most generic method but does best under the most
conditions.
Virus Behavior Allows for Effective Gene Transfer. Biomedical engineer Joseph M. Le Doux expresses hope in the use of viruses as an in-vivo vector in his book Gene Therapy Protocols Vol 1: Production and In Vivo Applications of Gene Transfer Vectors (2008). Several passages and collections of academia in the book point to viruses as being highly effective in passing on genetic information. So much so that over half of the vectors used in trials are viral as seen in Figure 1.
Figure 1
Proof of Viral Vectors Being Used Most in Clinical Trial [Vectors Used in Gene Therapy Clinical Trials (2009), Journal of Gene Medicine]
http://www.abedia.com/wiley/images/0809vectors.jpg
This is because of their natural behavior. Viruses are designed to release the gene encoded proteins onto a living organism so that they may then carry those traits (Le Doux, 2009). The same behavior which allows them to easily transfer disease can allow them to transfer specific genetic materials. As stated by the American Cancer Society’s research into gene therapy “…viruses have some special properties that make them useful tools in gene therapy. Viruses reproduce by ‘hijacking’ infected cells. They inject their genes …into the cells they infect” (2009). This then allows a cell’s nucleus to produce the wanted genes. Figure 2 shows a picture of the capsulated region of the virus that can be outfitted with accommodating genes once the disease causing pathogens have been removed.
Figure 2
Virus with Capsid [Nobelprize.org]
http://nobelprize.org/nobel_prizes/medicine/laureates/1993/illpres/big-adenovirus-v3.gif
Adenovirus Vectors
Reduce Risk of Viral Infection. There are fears that introducing a virus
into one’s system may be harmful if the virus is treated as a pathogen by the
body. Adenoviruses are easily “gutted” of disease causing agents leaving few if
any trace (Le Doux, 2009). The body is then less likely to attack a cell that
appears to not show any chance of doing harm.
Point 2: Heavy Focus on Single Gene Disorders
Obviously the ultimate goal of
finding the most suitable vector for gene transfer is to be able to promote
gene therapy practices with minimum risk. This can only be done after clinical
trials of which the focus should first be on single gene disorders.
One Step at a Time. Gene
therapy is fairly new compared to other forms of medicine so it is necessary to
start with little incremental steps. The first of which after finding a
suitable viral vector is to focus on single gene therapy. Single gene therapy,
which is gene modification directed towards disorders that affect only a single
gene, is in theory a lot simpler than multigene therapy for obvious reasons
(Foti, S., Samulski, R., McCown, T. 2009). Foti, Samulski, and McCown point out
that most vectors have a limited carrying capacity and that the complexities of
multigene disorders make it too difficult to craft needed treatments right now
(2009). A compromise may be to first and foremost focus on modification
techniques just for one individual gene. By focusing on one gene at a time
there is less risk of complications. Once individual genes are studied then
there results can be combined in an attempt to deal with multigene disorders. This
process can be a lot slower but should be more effective as expressed by Le
Doux (1999).
Effects of Single Gene
Therapy. Single gene therapy has had its share of breakthroughs in the lab
but more needs to be done with clinical trials.
Progress with animals.
All gene therapy trials that involve living organisms generally have to be
tested in animals for obvious reasons. Although there has been some controversy
concerning animal testing, there has been no other more effective way to test
gene therapy without possible harm to humans (Human Genome Project Information,
2009). Luckily such controversy has been overshadowed by significant advances. Dr. Brooks-Kayal and Dr. Shelley J. Russek
of University of Pennsylvania and Boston University, respectively, have been
able to reduce epilepsy in mice by modifying signal pathways in their brains
associated with genes (Medical News Today, 2006). In 2001, scientists from
Progress with humans. A
number of single gene modification trials, which have been debatably considered
low risk, are being done with human subjects (Guidance for Industry: Gene
Therapy Clinical Trials - Observing Subjects for Delayed Adverse Events).
The complication risk associated with the actual gene is said to be reduced
with single gene trials in conjunction with the lower risk of complications
linked to use of adenovirus vectors. As stated best by the Federal Food and
Drug Administration “…adenovirus [vectors]…do not have a propensity to
integrate or reactivate following latency and, in the absence of evidence to
the contrary, present a low risk of gene therapy-related delayed adverse
events” (Guidance for Industry: Gene Therapy Clinical Trials - Observing
Subjects for Delayed Adverse Events) . Although there have been a limited
number of trials with humans with even less significant accomplished test,
progress is being made. The
Point 3: Venturing into Multigene Therapy Treatments
As science and technology advance with simpler gene therapy techniques, more can be done concerning multigene disorders. Point three is based mostly on research in progress and studies that may be done in the future with the proper support. It was decided to include this section as an outlook of possible treatments to come if appropriately sustained. Multigene ailments include but are not limited to heart diseases, diabetes, Alzheimer’s, and multiple types of cancer. However; there have been advances in gene therapy treatments as to cancer in animal subjects (Human Genome Project Information, 2009). A lot of this has to do with the extra funding for cancer research and how cancer reacts differently than most other cell types. Treatments range from replacing altered genes susceptible to cancer with healthy ones to using altered genes to try to improve patient immune response (National Cancer Institute, 2006).
Disclaimer/Ethical
Response
Just as with any other medical treatment undergoing testing, serious precautions need to be made. It is recommended that the NIH set up an ethical review board exclusively for gene therapy human trials. This will ensure that all research results produce bona fide facts, whether favorable or not. With this in mind, human clinical trials, especially for multigene disorders, should be tested sparingly with priority given to terminally ill patients until further research. Precautions should also be taken to ensure patients’ privacy and patient must have a clear understanding of the risk. It should be advised that gene therapy is a last resort procedure until further research. Complications include rejection of DNA carriers and negative immune response (Human Genome Project, 2009). Most of what have been called successes in gene therapy has happened just over the last couple years. As with any invasive medical procedure, death is possible but should be reduced with more animal trials and understanding. Excessive measures should be taken concerning muscular dystrophy gene modification treatments to avoid gene “doping” which has been defined as “non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance” by Gene Therapy Net (2009).
Conclusion
Based on research presented and
research in progress, it is clear that many diseases that affect the genes can
be best treated with gene therapy. Because of this, more support should be
given to research and funding of gene therapy trials, especially by a world
renown organization like the NIH. It is recommended that the NIH support this
field to allow for productive growth and valuable supervision which is not
available elsewhere. Gene therapy shows the most promise when following the
three points listed above and procedures briefly summarized in Figure 3.
Figure 3
How Viral Vectors Transfer Genes [Elements4Health]
http://www.acceleratingfuture.com/michael/blog/images/Gene_therapy.jpg
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