RESEARCH PROPOSAL

Alessandra Leone
Independent Research I G/T
2016-2017
Title: Gene therapy: The Clot Thickens

Introduction and Overview of Research:

This research project is focused on gene therapy, specifically on evaluating the efficiency
of various viral vectors in order to minimize risks in using it as a treatment option for hemophilia
B. By creating a recommended solution to this problem, there will be less risk and more chances
of success for human gene therapy trials when being conducted to treat hemophilia B. This
would also be a step in the process of finding a way for gene therapy to be more safe and
effective in order to be approved for widespread use for patients of monogenic diseases.

Background and Rationale:

Gene therapy, first introduced in the 1960s, has been a controversial form of treatment for
some time. Many studies have been conducted, but so far it hasnt been definitively proven a safe
and effective treatment. Gene therapy is an experimental technique of utilizing DNA to combat
defective and diseased genes. It can be done via an injection or an IV. To inject the gene
treatment into the patient, the gene is first often carried in viruses, so that they can be delivered
to the cell through infection (How does gene therapy work?). For hemophilia B, St. Jude
Hospital clinical gene therapy trials showed that the patient's amount of factor IX increased 30%.
While this is only a minimal increase, such small changes carry great impact on the patients
lives, as it can transform the symptoms and severity. However, 40% of the patients had virus
antibodies which blocked the treatment (University of Oxford). In order to reduce these risks and
heighten efficiency, different viral vectors should be explored as options. Adenoviruses infect the
target cell very effectively, and are more well known as the common cold virus. However, the
expression of therapeutic gene fades, while with retroviruses, there is a more long lasting effect,
but these vectors have a risk of disrupting cell division and causing tumor growth. Associated
adenoviruses dont have the risk of an immune response because it's a harmless virus usually
already in our systems, but they need a helper virus to replicate themselves. Adenoviruses
triggered lethal immune system reactions, while retroviruses provoked cancer (Panno, J)

This is an important topic because if gene therapy works correctly, it will signify
enormous scientific and technological advancements for contemporary society. The implications
of this would change methods of scientific research and impact the world as it progresses. By
focusing on hemophilia B, the effect it specifically has on genetic diseases can be explored.
Furthermore, by comparing the variations in the outcomes of studies that used different vectors,
I can analyze the overall effect on the treatment, and draw a concrete conclusion on their efficacy
with a recommended solution. The main issue with gene therapy preventing it from widespread
use is the risks of gene delivery. If the viral vectors could be specialized for certain diseases and
analyzed for the most suited, this could help eliminate some problems found in current clinical
trials with human gene therapy.

Research Methodology:
Research Question:

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Which viral vector is most efficient in delivering therapeutic genes as treatment for hemophilia
B?
Research Hypothesis:
The adeno-associated virus is most efficient in gene delivery compared to other viral vectors in
relation to hemophilia B. In my synthesis paper, I will support my claim by finding various
studies which used different vectors and use statistics from the results to form my conclusions on
their efficiencies.
Research Design Model:
Evaluation is the best design approach to my research, as I am investigating the differences
between viral vectors and which is most efficient with hemophilia B. This is a mixed methods
design, therefore incorporating quantitative and qualitative elements into my research process.
The variables in my study will be the adenovirus, the retrovirus, and the adeno-associated virus.
These are all different types of DNA viruses, which are composed of DNA surrounded by a
protein coat.
Data Collection:
Meta analysis will be conducted for original data collection because gene therapy is based on
complex biotechnology which is unaccessible, creating difficulties in conducting an authentic
experiment. Instead, through access to raw data from other studies, information can be gathered
to draw analytical conclusions relating to the research question. By collecting data from
published research studies that use various viral vectors on hemophilia B, it can be concluded
which vehicle has the greatest efficiency. Most studies research whether

Product Objectives:
In order to showcase the information collected, a brochure could be created which
informs the audience of what gene therapy is, how its being implemented as treatment, and the
implications of these advancements. This product is targeted towards high school students, as
they are the most easily accessible population. The research will specifically communicated to
advanced science classes, as the students in these classes have a higher scientific literacy and are
able to understand and have more interest in the topic. They will already have background
information on genetics and be able to put this information into the context of their learning.
These brochures can be distributed to science classes around the school.
Logistical Considerations:
For the product, large quantities of paper are needed in order to create the amount of
brochures needed for distribution. Permission would also need to be obtained from the science
teachers at Mt. Hebron to leave the brochures in their classrooms. In third quarter, a timeline will
be added that outlines the data collection, product development, and audience distribution.

Timeline:
The researcher has compiled meta analysis articles and interview questions to utilize for data
collection. They have also composed a review of current literature for research, and will continue
with data collection to finalize the synthesis paper.
Compile meta analysis articles (February)
Create list of interview questions for experts (February)
Data collection approval in third quarter conference (February)
Write first drafts of review of literature (February)

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 Contact adviser for more meta analysis articles which are inaccessible to students
(March)
Edit review of literature and peers paper (March)
Finalize review of literature for synthesis paper (March)
Collect all data for analysis (April)
Complete data analysis and prepare for review (April)
Add data collection to synthesis paper and edit (April)
Email adviser to check synthesis paper for approval (April)
Compose abstract clarifying the research (April)
Finalize synthesis paper and submit (April)
Construct a display board of research (May)
Create final product of brochure (May)
Ask for approval to distribute in biology high school classes (May)
Collect and respond to audience evaluation of final product (May)
Create a PowerPoint summarizing research to introduce AP Biology students to
gene therapy (May)
Ask Ms. Stafford for opportunity to present research in her 4A class (May)
Schedule date of oral presentation (May)
Submit brochure (May 31st)
Complete an online and paper portfolio (June)

Approval:

____________________ _________________________
Student Signature G/T Resource Teacher Signature

References:
Panno, J. (n.d.). Gene therapy: Treating disease by repairing genes. NY: Facts
on File.
How does gene therapy work? (2016, October 18). Retrieved from
https://ghr.nlm.nih.gov/primer/therapy/procedures
University of Oxford. (2015, January 8). Gene therapy for cancer and other
diseases [Video file]. Retrieved from https://www.youtube.com/ watch?
v=M_plg10Hn6E&list=PLSnUdyQgziZtlDwoVzVIHM4EDegePO3mE&index=4