Standort in Deutschland, wo man günstige und qualitativ hochwertige Kamagra Ohne Rezept Lieferung in jedem Teil der Welt zu kaufen.
Kaufen priligy im Online-Shop.
Wirkung ist gut, kommt sehr schnell, innerhalb von 5-7 Minuten. cialis was nur nicht versucht, verbrachte eine Menge Geld und Nerven, und geholfen hat mir nur dieses Tool.
Antiretrovirals - klöhn
Producing antiretroviral drugs in plants
In 1983 Luc Montagnier who worked at the Pasteur Institute in France
discovered that the acquired immune deficiency syndrome (AIDS) is caused by
a retrovirus that is nowadays known as the human immunodeficiency virus
(HIV). According to estimates of the Joint United Nations Program on
HIV/AIDS (UNAIDS) and the World Health Organization (WHO) 25 million
people have died of the disease so far (wikipedia.org). Montagnier´s work
provided a basis for research concerning the treatment of AIDS and scientists
started immediately looking for drugs with an effect on the virus. In 1985 a
group of scientists at the National Cancer Institute discovered that the drug
Zidovudine has an impact on the virus by reducing the viral load. Today
Zidovudine is one of several known antiretroviral drugs that are used in
combination therapies. HIV-carriers in developed countries benefit from these
therapies whereas the considerable number of AIDS-infected people in
developing countries cannot afford the costs of the drugs. Producing
antiretroviral drugs in genetically modified plants is a way to approach this
The HI-virus is a spherical retrovirus with a diameter of about 120 nm that can
be transferred in blood, semen, vaginal fluid and breast milk. Inside the virus
particle there is a capsid that consists of two protein components and contains
the single stranded RNA-genome. The genome contains 9000 nucleotides that
encode for nine genes. In addition the virus particle contains the enzymes
reverse transcriptase, protease and integrase. The capsid is surrounded by a
membrane that is composed of a lipid bilayer and transmembrane proteins
gp120 and gp41. An infection begins with the specific binding of gp120 to
receptors within human CD4 T-cells. The glycoprotein gp41 promotes the
fusion of the virus envelope and the host cell. This process enables viral RNA
to enter the host cell where the RNA is translated into complementary DNA
(cDNA) by viral reverse transcriptase. The process of integration of the viral
cDNA into the human genome is catalyzed by the enzyme integrase. The
cDNA encodes for viral proteins that are transcribed and translated by human
enzymes. The newly formed viruses are released and infect more CD4 T-cells
hence the number of CD4 T-cells is reduced during an HIV-infection. As the
CD4 T-cells are important parts of the human immune system, their decimation
causes a loss of the body’s defences. Due to the fact that reverse transcriptase
has no proofreading function mutations occur 106 times more often during
transcription of viral RNA than during transcription of human DNA
(bio.classes.ucsc.edu). Therefore the genome of the HI-virus is not stable. That
is why up until now the development of an effective preventive antiretroviral
drug has failed. But there are several post-infection drugs on the market that
These antiretroviral drugs can be divided into the following groups as they
interfere with the process of infection at different stages: entry inhibitors,
protease inhibitors, fusion inhibitors, integrase inhibitors and reverse
transcriptase inhibitors. These drugs are used in a combination therapy called
HAART (highly active antiretroviral therapy). A few years ago the diagnosis of
AIDS was a death sentence and the patient had a life expectancy of about two
years after diagnosis. Due to antiretroviral drugs that reduce the viral load, this
situation has changed and life expectancy has risen to more than twenty years
after infection. But only HIV-carriers in developed countries can benefit from
this progress whereas most of the HIV-carriers in developing countries cannot
afford the costs of antiretroviral drugs.
At the present time antiretroviral drugs are produced by chemical synthesis.
The synthesis can only be accomplished in modern factories in developed
countries as it is a high-tech process. The high costs of production are reflected
in the price for antiretroviral drugs. The costs of medical care for a HIV-patient
add up to $2,100 per month or $618,000 in a lifetime
(nytimes.com). Hence only HIV-carriers in developed countries can afford the
money for an adequate treatment of the disease.
Only every tenth AIDS-infected person lives in a developed country whereas
90% of all HIV-carriers live in developing countries. Sub-Saharan Africa is the
worst effected region with about 25 million people living with the virus. Only
810,100 HIV-carriers in Sub-Saharan Africa receive antiretroviral therapy
(hivinsite.ucsf.edu ). Thus the mortality after an HIV-infection in
developing countries is much higher than it is in developed countries. One of
the few practical solutions to approach the problem is to lower the costs of
production as it would bring down the price of the product to make it
affordable for people living in developing countries.
The use of genetically modified plants as production platforms could help to
bring down the costs of production as it is an inexpensive process. The first
plant-derived pharmaceutical enzyme was human serum albumin that was
produced in transgenic tobacco (Sijmons et al, 1990). Genetic modification of
plants has been further developed in recent years so it is nowadays possible to
transform a wide range of plants and the first technical proteins produced in
genetically modified plants are sold. Experiments regarding the production of
antiretroviral drugs focus on the use of maize, wheat, tobacco, barley and rice
plants as production platforms because they have the following advantages. All
of these plants are easily transformable and produce reasonable amounts of the
product in a short period. Moreover most of these plants can be grown in
developing regions such as South and South East Asia or South America, as
their climatic environmental requirements are similar to the climate in these
regions. Maize plants can store recombinant proteins in their seeds if the gene
encoding for the product is connected with a promoter for storage proteins.
Stored in the seed the protein is stable for many years. To use tobacco for the
production of drugs is advantageous because tobacco can produce reasonable
amounts of the product which is located in the leaf. In addition tobacco is a
non-food crop therefore there is no danger for unintentional uptake of
antiretroviral drugs produced in the plant.
Compared to chemical synthesis of antiretroviral drugs the production in plants
is a low-tech process. Therefore the process could not only be conducted in
pharmaceutical plants in developed countries but also in developing countries.
This would guarantee that the drugs come on the market where they are
required and it would save transportation charges.
Another advantage of producing antiretroviral drugs in plants is the fact that
reasonable amounts can be produced. The fact that only 2% of all HIV-carriers
receive antiretroviral drugs shows that the current amount of drugs produced
by chemical synthesis is not enough to meet the demand (hivinsite.ucsf.edu
Examples for antiretroviral drugs producible in plants are the HIV neutralizing
antibodies 2F5 and 2G12. These antibodies bind to the glycoprotein gp41
which is essential for the fusion of the virus membrane and the host cell. If an
antibody is bound to the gp41 the infection is interrupted hence 2F5 and 2G12
belong to the group of fusion inhibitors.
In 1989 the first antibodies have been produced in tobacco plants (Hiatt et al,
1989). Antibodies are complex proteins that consist of four subunits. Producing
antibodies in plants is possible as plants are able to perform complex protein
folding, whereas most bacteria are only able to synthesize simple proteins. Not
only the correct folding but also post-translational modifications such as N-
glycolisation are performed in plants. This argues for the use of plants as
production platforms instead of bacteria. Another advantage of producing
drugs in plants is the fact that phytopathogenic viruses are no danger for human
beings. Therefore there is no risk of an infection whereas bacteria and animal
cells used in a production process can carry viruses that infect humans.
Although using plants to produce antiretroviral drugs offers lots of advantages,
there are safety issues that have to be considered. Of course the risk of escape
of transgenic pollen has to be minimized to ensure that antiretroviral drugs do
not enter the food chain. This can be accomplished in different ways. For
example the production can be carried out in greenhouses. According to
estimates the required amount of hepatitis B virus could be produced on 250
acres of greenhouse space (Ma et al, 2005). This demonstrates that it is
possible to produce reasonable amounts in the controlled environment of
greenhouses. Another way to control genetically modified plants is to mark
them. The gene for the marker has to be linked to the gene for the antiretroviral
drug. Examples for markers that can report transgenic activity are fluorescent
proteins such as the green fluorescent protein or DsRed that are derived from
When it comes to the production of antiretroviral drugs in plants these safety
aspects have to be taken into consideration by manufacturing companies to
avoid unintentional uptake of drugs and the escape of transgenic pollen, plants
or seeds that could affect the gene pool of wild species.
Using plants as production platforms to increase the amount of antiretroviral
drugs could help to meet the demand for antiretroviral drugs of 40 million
AIDS-infected people worldwide. HIV-carriers in developing countries could
benefit from the low costs of production that affect the price for medication.
The effect of the drugs is shown by the decrease of mortality after an infection
in developed countries. However the mortality after an infection is stagnating
in developing countries. UNAIDS, the program of the United Nations,
estimates that if the number of people having access to antiretroviral drugs
does not increase there will be 6.5 million dying of the disease in 2030,
compared to 2.8 million in 2002 (unaids.org).
References: bio.classes.ucsc.edu: http://bio.classes.ucsc.edu/bio175/F06_175_lecture2.pdf, retrieved/accessed December 28, 2006. Hiatt, A., Cafferkey, R. and Bowdish, K. (1989): Production of antibodies in transgenic plants. Nature, 342, 76−78. hivinsite.ucsf.edu , :
http://hivinsite.ucsf.edu/global?page=cr09-00-00&post=20&cid=AOX, retrieved/accessed December 28, 2006.
Ma, J., Barros, E., Bock, R., Christou, P., Dale, P., Dix, P., Fischer, R., Irwin, J., Mahoney, R., Pezzotti, M., Schillberg, S., Sparrow, P., Stoger, E., Twyman, R. (2005): Molecular farming for new drugs and vaccines. EMBO reports, 6, 594. nytimes.com: http://www.nytimes.com/2006/11/12/us/12hiv.html?ex=1165554000&en=a52ed7be905cda7&ei=5070, retrieved/accessed December 11, 2006. Sijmons, P., Dekker, B., Schrammeijer, B., Verwoerd, T., van den Elzen, P., Hoekema, A. (1990): Production of correctly processed human serum albumin in transgenic plants. Bio/Technology, 8, 217 – 221. unaids.org: http://www.unaids.org/en/HIV_data/epi2006/default.asp, retrieved/accessed December 28, 2006. Wikipedia.org: http://en.wikipedia.org/wiki/Hiv, retrieved/accessed December 28, 2006.
CullenaghPortlaoiseCo. Laois20th January 2011Thank you for forwarding a copy of Tony Holohanʼs letter regarding Gardasil vaccination and thank you for taking the time to consider my argument on this important subject. I would like to lay out my reply to Dr. Holohan quite simply in this letter and I would also like to backup my statements with relevant references and additional information below
Effect of temperature on the selectivity of sulfonamides and trimethoprim on a carbon clad zirconium dioxide column S. Giegold1,2, Thorsten Teutenberg1J. Tuerk1, T. K. Kiffmeyer1 , B. Wenclawiak21Institute of Energy and Environmental Technology (IUTA), Bliersheimer Straße 60, D-47229 Duisburg, Germany; 2University of Siegen, D-57068 Siegen, Germany Introduction The use of high tem