From: Subject: Tobacco plant-made therapeutic thwarts West Nile virus Date: Tue, 9 Feb 2010 10:39:37 -0800 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_000D_01CAA974.2D92B410" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_000D_01CAA974.2D92B410 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.sciencedaily.com/releases/2010/02/100201171643.htm Tobacco = plant-made therapeutic thwarts West Nile virus
3D"ScienceDaily:

Tobacco Plant-Made Therapeutic Thwarts = West Nile=20 Virus

ScienceDaily (Feb. 3, 2010) =97 = A new=20 therapeutic made from tobacco plants has been shown to arrest West Nile = virus=20 infection, according to a new study by Arizona State University = scientist Qiang=20 Chen and his colleagues.

Chen, a researcher at Arizona State University's Biodesign Institute = and=20 professor in the PolyTechnic Campus' College of Technology and = Innovation, is=20 the first to demonstrate a plant-derived treatment to successfully = combat West=20 Nile virus after exposure and infection. The research appears in the=20 Proceedings of the National Academy of Sciences (advanced = online=20 edition).

There are currently no available vaccines against West Nile, nor = effective=20 therapeutics for human use, so the current findings are a considerable=20 advancement and may offer the best hope thus far that the West Nile = virus=20 infection can be stopped, even several days after viral infection.

West Nile virus has made alarming inroads in North America, causing = disease=20 outbreaks throughout the U.S., as well as in areas of Canada, Mexico, = the=20 Caribbean and South America. Elderly individuals and those with = depressed=20 immunity are particularly vulnerable to West Nile, a mosquito-borne = illness=20 which can cause a potentially lethal inflammation of the brain.

Chen's group demonstrated the versatility of plant-based = biotechnology. "The=20 goal of this research was twofold," said Chen. "First, we wanted to show = proof-of- concept, demonstrating that plant-made antibodies can work as=20 effective post-exposure therapeutics. Secondly, we've sought to develop = a=20 therapeutic which can be made inexpensively so that the health care = systems in=20 developing countries can afford it."

Issues of affordability for such antibody-based treatments are = central to the=20 challenge, Chen stresses, with the costs for development of a = traditional=20 pharmaceutical mammalian cell line production facility often running = into the=20 tens of millions of dollars. Besides being inexpensive, plants offer = other=20 advantages. Mammalian cell lines may run the risk of harboring animal = pathogens=20 such as viruses or infectious protein agents known as prions, not found = in=20 plants. Plants also allow production of pharmaceutical products to be = easily=20 scaled up to whatever quantities are required. "With mammalian cells = systems,=20 the physical size of the bioreactor is limiting," said Chen, "whereas = with=20 plants, we can just plant another acre."

The study examined antibodies against West Nile virus derived from = mammalian=20 cell lines and compared their effectiveness with those extracted from = plants.=20 The plants used to produce the antibodies are a relative of common = tobacco, a=20 member of the Solanceae family of plants, which produce = abundant leaves=20 for harvesting material and are also prolific seed producers. Seven days = after=20 the introduction of antibody genes into plants, the leaves are = harvested,=20 homogenized and purified to remove extraneous material.

The strategy for gene insertion is to use the specific machinery of = the=20 tobacco mosaic virus and potato virus X (PVX) to carry the genes of = interest=20 into the plants, where they can be expressed, yielding a human = monoclonal=20 antibody known as hu-E16. The gene expression occurs in just a week's = time,=20 making the production process highly efficient.

The monoclonal antibody, once injected into the recipient, binds to a = particular surface protein of the virus. That binding site is also the = one used=20 by the virus to attach itself to mammalian host cells, and once it is = occupied,=20 the virus' cell-binding (and infectious) capacity is neutralized.

Cell-derived versions of this antibody have already demonstrated = impressive=20 effectiveness, protecting mice from WNV-induced mortality even several = days=20 after infection. Chen's research shows comparable effectiveness using=20 tobacco-plant derived monoclonal antibodies. Indeed, the results in the = groups=20 of mice tested, were essentially indistinguishable. The therapeutic, = Chen=20 emphasizes, is effective in very small dosages, (50-200 micrograms), and = only=20 one dose is required to clear the virus from an infected individual's=20 system.

The effectiveness of the plant expression system is dependent in part = on the=20 optimization of the antibody DNA sequence, which helps to ensure a high = level of=20 expression in the plants. "The goal is to make more of the protein and = for it to=20 persist longer before it is degraded, " said Chen. "Optimization helps." = The=20 strategy permitted the group to set a record for the antibody yield = produced by=20 the transgenic tobacco plants -- an increase from 500 micrograms of = antibody per=20 gram of leaf tissue to 800 micrograms per leaf.

Because the monoclonal antibody therapeutic binds to a conserved = region of=20 the viral surface, it can be effective against a variety of West Nile = virus=20 stains and potentially against other flaviviral strains. Here, another = advantage=20 of plant-derived as opposed to animal-derived antibodies becomes = important. If=20 an individual is exposed to a variant strain of virus differing in some=20 particulars from the antibody used to treat it, there is a chance in the = case of=20 the mammalian cell-derived therapy to actually worsen the condition, = through an=20 effect known as antibody dependent enhancement. The process has been = studied in=20 some detail in dengue fever, a related flavivirus. Chen emphasizes that=20 plant-based antibodies lack the capacity to bind with a critical = receptor=20 implicated in the antibody dependent enhancement effect, making them = potentially=20 safer for use.

The completion of this research relied on the efforts of a large,=20 interdisciplinary team, including lead author Huafang "Lily" Lai. = Michael=20 Diamond of Washington University collaborated in studies with the mouse = model.=20 In addition to Chen's ASU scientist colleagues, Thomas Keller, an = undergraduate=20 in ASU's School of Life Sciences Undergraduate Research program appears = as a=20 co-author of the PNAS paper, having carried out much of the critical = protein=20 expression and characterization work. "This was a very remarkable = achievement=20 for an undergraduate student," Chen points out. The research was = supported by=20 grants from the National Institute of Allergy and Infectious Diseases, = and=20 Keller's work was supported in part through the Howard Hughes Fellowship = for=20 Undergraduate Research.

While the group's focus has been on West Nile Virus, Chen believes = the=20 plant-based antibody approach could provide highly effective, cost = efficient=20 therapeutics for other diseases, including related flavivirus infections = such as=20 dengue fever and Japanese encephalitis, if the successes in mice can be=20 replicated in humans.

One challenge in treating a virus like West Nile, which targets the = central=20 nervous system, is that current antibody therapeutics are unable to = pursue the=20 virus into its sanctuaries in the human brain, due to the existence of = the blood=20 brain barrier. If this obstacle can be overcome, it may be possible to = produce=20 therapeutics capable of eradicating the infection even after 6 or 7 = days, when a=20 significant amount of virus has colonized brain tissue.

Toward this end, Chen is now working on bifunctional antibodies, = capable of=20 binding with virus particles as well as attaching to receptors in the = brain,=20 allowing the antibody to migrate past the blood brain threshold. If = successful,=20 the technique may allow treatment of other, currently intractable = infectious and=20 neurological diseases. "If we can find a way to deliver therapeutics of = this=20 sort into the brain it will be really significant," said Chen.

Email=20 or share this story:
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Story Source:

Adapted from materials provided by Arizona = State=20 University. Original article written by Richard Harth, = Biodesign=20 Institute science writer.
=20
APA

MLA =

Note: If no author is given, the source is cited=20 instead.

enlarge
3D""=20
Qiang "Shawn" Chen and lead author Huafang "Lily" Lai = arrested=20 West Nile virus infection with a new therapeutic manufactured from = tobacco=20 plants. (Credit: Barb Backes, Biodesign Institute at = ASU)

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WIDTH: 180px; PADDING-RIGHT: = 10px; FONT-SIZE: 13px; OVERFLOW: hidden; PADDING-TOP: 5px } #googlehome DIV { PADDING-BOTTOM: 5px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; OVERFLOW: = hidden; PADDING-TOP: 5px } #googlehome DIV.left { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; FLOAT: = left; FONT-SIZE: 11px; PADDING-TOP: 0px } #googlehome DIV.right { TEXT-ALIGN: right; PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; = PADDING-RIGHT: 0px; FONT-SIZE: 11px; PADDING-TOP: 0px } #googlehome DIV.clear { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; CLEAR: = both; PADDING-TOP: 0px } #googletop { MARGIN: 0px 0px 10px; FONT-SIZE: 13px } #googletop DIV { OVERFLOW: hidden } #googletop DIV.left { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; FLOAT: = left; FONT-SIZE: 11px; PADDING-TOP: 0px } #googletop DIV.right { TEXT-ALIGN: right; PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; = PADDING-RIGHT: 0px; FONT-SIZE: 11px; PADDING-TOP: 0px } #googletop DIV.clear { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; CLEAR: = both; PADDING-TOP: 0px } #googletop DIV.col1 { PADDING-BOTTOM: 5px; PADDING-LEFT: 0px; WIDTH: 164px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googletop DIV.col2 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 164px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googletop DIV.col3 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 164px; PADDING-RIGHT: = 0px; FLOAT: right; PADDING-TOP: 5px } #googleend { MARGIN: 0px 0px 10px; FONT-SIZE: 13px } #googleend DIV { OVERFLOW: hidden } #googleend DIV.left { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; FLOAT: = left; FONT-SIZE: 11px; PADDING-TOP: 0px } #googleend DIV.right { TEXT-ALIGN: right; PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; = PADDING-RIGHT: 0px; FONT-SIZE: 11px; PADDING-TOP: 0px } #googleend DIV.clear { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; CLEAR: = both; PADDING-TOP: 0px } #googleend DIV.col1 { PADDING-BOTTOM: 5px; PADDING-LEFT: 0px; WIDTH: 164px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googleend DIV.col2 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 164px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googleend DIV.col3 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 164px; PADDING-RIGHT: = 0px; FLOAT: right; PADDING-TOP: 5px } #googlebottom { MARGIN: 20px 0px 10px; WIDTH: 678px; FONT-SIZE: 13px } #googlebottom DIV { OVERFLOW: hidden } #googlebottom DIV.left { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; FLOAT: = left; FONT-SIZE: 11px; PADDING-TOP: 0px } #googlebottom DIV.right { TEXT-ALIGN: right; PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; = PADDING-RIGHT: 0px; FONT-SIZE: 11px; PADDING-TOP: 0px } #googlebottom DIV.clear { PADDING-BOTTOM: 0px; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; CLEAR: = both; PADDING-TOP: 0px } #googlebottom DIV.col1 { PADDING-BOTTOM: 5px; PADDING-LEFT: 0px; WIDTH: 210px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googlebottom DIV.col2 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 220px; PADDING-RIGHT: = 5px; FLOAT: left; PADDING-TOP: 5px } #googlebottom DIV.col3 { PADDING-BOTTOM: 5px; PADDING-LEFT: 5px; WIDTH: 210px; PADDING-RIGHT: = 0px; FLOAT: right; PADDING-TOP: 5px } #share_form { Z-INDEX: 999; BORDER-BOTTOM: #999 1px solid; POSITION: absolute; = BORDER-LEFT: #999 1px solid; WIDTH: 300px; DISPLAY: none; BACKGROUND: = #eee; BORDER-TOP: #999 1px solid; BORDER-RIGHT: #999 1px solid } #share_title { MARGIN: 5px; WIDTH: 60%; FLOAT: left } #share_close { FONT-STYLE: italic; MARGIN: 5px; FLOAT: right } #share_close A { COLOR: #009; TEXT-DECORATION: none } #share_close A:hover { COLOR: #900; TEXT-DECORATION: none } #share_form DIV.clear { FLOAT: none; CLEAR: both } #share_social { PADDING-BOTTOM: 5px; PADDING-LEFT: 7px; PADDING-RIGHT: 10px; = BACKGROUND: #fff; PADDING-TOP: 5px } #share_social UL { PADDING-BOTTOM: 0px; LIST-STYLE-TYPE: none; MARGIN: 0px; PADDING-LEFT: = 0px; PADDING-RIGHT: 0px; LIST-STYLE-IMAGE: none; PADDING-TOP: 0px } #share_social UL LI { PADDING-BOTTOM: 0px; 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