CHANGE will revolutionize AIDS treatment; it will overcome all of
today’s obstacles.
Certain humans and simians who have been found to carry the HIV virus were
able to naturally suppress it. Rare genetic mutations give them this
ability. These genes both increase and strengthen immune response
against HIV. Furthermore, they effectively halt its replication. Through
extensive research, these genes have been identified.
CHANGE plans to use a safe, easy gene therapy route in curing AIDS.
The basis of this gene therapy is to replace defective or harmful
genes with improved ones. CHANGE utilizes viruses, which are naturally
able to transfer their DNA into a cell. In this case, they will be
used to deliver genes that grant a person immunity from AIDS.
The foundation of our project is the ability to incorporate
AIDS-resistant genes into viral vectors which will enter stem
cells and multiply. To do this, we must first isolate the pertinent genes
from simian and human cells.
Restriction enzymes will cut the genes at nucleic acid sequences corresponding to
the ends of the genes. Through a commonly used DNA amplification
method, polymerase chain reaction (PCR), the genes can be multiplied.
PCR uses a protein, DNA polymerase, to amplify a DNA
sequence using a template, which in this case, is the CHANGE gene.
Finally, the CHANGE gene can be incorporated into viral vectors. We then cut
both the isolated CHANGE gene and the viral genes with the same
restriction enzyme. This creates “sticky ends” on both the viral
vector genome and CHANGE gene. In other words, the enzyme cuts the
genes in such a way that they have complementary bases. Thus, when
they are in the presence of each other and DNA ligase, the CHANGE gene
fuses with the viral enzyme. We now have a viral vector loaded with
the CHANGE genes, ready to be inserted.
Through a simple injection into the pelvis, a significant source of stem
cells, the virus containing the CHANGE genes are released. By way of
endocytosis, the genes enter the stem cells. There, the genes can
safely incorporate themselves into the stem cells' genome. Rapidly
dividing stem cells will give birth to billions of macrophages and
T-cells, replacing the entire immune system with HIV resistant cells,
thus curing the patient.
Click “Play” to view an animated explanation of the CHANGE gene’s
incorporation into the cell.
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Our prototype is illustrated above. The following is a brief description of it.
In a typical human, HIV is able to bypass all of the body’s defenses,
enter the immune cells, and incorporate its viral DNA. After doing so,
it is able to use the cell’s mechanisms to reproduce other HIV
viruses, spreading HIV throughout the body.
When our adeno-associated virus enters the cell, it is able to easily
integrate the CHANGE genes into the cell’s genome. By doing so, it is
able to provide resistance against future HIV attacks.
Before HIV integrates into the cell’s genome, it must first dissemble its
capsid and then release the viral DNA. One of the CHANGE gene codes for a
protein in simians, TRIM5alpha, which binds to the HIV virus, stopping
it from disassembling its capsid. Therefore, HIV is rendered harmless,
unable to infect the cell.
The other CHANGE genes, HLA-A*6802, HLA- B18, and HLA-C rs9264942
increase the strength and effectiveness of the immune response against
HIV. First, the genes give a larger, speedier immune response.
Also, the effectiveness of the immune response is dramatically
increased. With the mutation, immune cells target important portions
of the HIV cell like gp120 and gp41, its binding proteins. This leaves
HIV incapable of entering the cell. Humans with these mutations have
been found to naturally suppress the HIV virus and live normal lives.