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   Biotech / MedicalNNVC - NanoViricides, Inc.


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From: donpat8/2/2006 2:10:58 PM
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Intracellular Tracking with Coated Gold Nanoparticles

Gold nanoparticles, with their novel optical and physical properties, have rapidly become a favorite tool of biomedical researchers, yet their ultimate utility in cancer research and clinical oncology depends on an ability to stably link them to targeting molecules and drugs. A new “bifunctional” coating that firmly attaches to the surface of gold nanoparticles while also providing an anchoring point for proteins and other molecules could overcome that limitation.

Mansoor Amiji, Ph.D., and colleagues at the Northeastern University Cancer Nanotechnology Platform Partnership have created a modified form of the biocompatible polymer poly(ethylene glycol) (PEG) to act as an all-purpose linker between gold nanoparticles and other molecules. In its native form, PEG has alcohol groups at each of its ends, and the Northeastern team had to solve the problem of converting only one of those alcohol groups into a thiol group, essentially swapping an oxygen atom for a sulfur atom. Sulfur forms tight chemical bonds with gold, while the remaining free alcohol group can create a chemical link to a wide variety of molecules.

The PEG molecule also acts as a spacer, affording enough distance between the gold nanoparticle and an attached protein, for example, so as to not interfere with the interaction of that protein with its biological target. In addition, PEG renders the particles invisible to macrophages, immune system cells that normally scavenge particles in the bloodstream, and prevents the gold nanoparticles from clumping in the bloodstream.

Having found a solution to this problem, the investigators used their bifunctional PEG to link a model fluorescent dye molecule to gold nanoparticles. They conducted toxicity assays with the resulting particles, finding that this construct was not toxic over a wide range of doses. The researchers then followed the nanoparticles, using fluorescence microscopy, as cells ferried the nanoparticles across their outer membranes and as the particles traveled within the cells. The researchers noted that the ability to attach a wide variety of molecules to the surfaces of gold nanoparticles and image them as they move through the cell should provide new tools for studying intracellular transport mechanisms.

This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery.” This paper is available free of charge through PubMed Central. View paper[http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=16467923 ].

nano.cancer.gov

Posted 2nd August 2006

azonano.com

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From: donpat8/2/2006 2:16:39 PM
   of 12865
 
Quantum leap for virus trackers

02 August 2006

Glowing quantum dots are helping researchers study how viruses infect cells, and although the fluorescent nanoparticles have only been used on plant viruses so far, the technique could prove to be invaluable for drug development.

The dots are made of tiny crystals of cadmium selenide, surrounded by a shell of zinc sulfide. Bogdan Dragnea, a chemist at Indiana University, Bloomington, US, leads the team that encapsulated these dots inside the protein coat that surrounds a virus, called the viral capsid.1

The great thing about quantum dots, said Dragnea, is their ‘remarkable photostability and brightness’. They shine brightly for a sufficiently long time (up to 10 minutes) to track what a virus is up to. The passage of the encapsulated quantum dots into a cell can be tracked using a confocal microscope, which produces sharper images than conventional microscopes by using a pinhole to exclude out-of-focus light.

Dragnea’s team adapted a technique they had developed to get gold nanoparticles inside viral capsids.2 The nanoparticle–capsid complex was built up by a self-assembly process, driven by the attraction between negatively charged gold nanoparticles and positively charged proteins that line the viral capsid. They believe this mimics the interaction between the anionic genetic contents and cationic protein coat in a real virus.

The researchers reasoned that other components, such as the glowing quantum dots, could be encapsulated like this if they had the same surface chemistry as the gold nanoparticles. Easier said than done.

Get your coat

Dragnea’s team studied four possible quantum dot coatings to find one that was suited to viral encapsulation. Using the wrong coating, or no coating at all, could make the nanoparticles insoluble, or alter the pH of the virus contents, which would halt the assembly process.

The researchers settled on a coating based on the long, floppy molecule polyethylene glycol (PEG), modified to carry a sulphur atom at one end and a carboxylic acid group at the other. This coating prepares the quantum dot for viral encapsulation, and also keeps the dot fluorescing for a relatively long time. The brightness of quantum dots coated with dihydrolipoic acid, for example, faded about eight times faster than the brightness of the PEG-coated dots.

Dihydrolipoic acid-coated quantum dots encapsulated in viral capsids are considerably less luminescent than QDs coated in polyethylene glycol

The viral capsids they studied were based on a well-understood plant virus, brome mosaic virus (BMV). It’s a useful starting point, said David Wright, associate professor of chemistry at Vanderbilt University, Nashville, Tennessee, US, although the technique will be more useful when it can be applied to less well understood, clinically relevant viruses.

But it could be invaluable for studying how long it takes for a particular virus to get across a cell membrane, or what route the virus takes, said Wright, who has stuck quantum dots to the outer coating of viruses to detect their presence in clinical samples.

Dragnea’s technique now needs to be applied to a range of viruses, said Wright: ‘it’s really going to be important to make it generalisable.’ Dragnea is now collaborating with biologists at Indiana University to study alphaviruses, which are responsible for a range of mosquito-borne human diseases.

Bea Perks

ReferencesS K Dixit et al, Nano Lett., 2006, (DOI: 10.1021/nl061165u)

B Dragnea et al, 2003, J Am Chem Soc, 125, 6374

Related Links
Nanotechnologists set viruses to work[http://www.rsc.org/chemistryworld/News/2006/February/21020601.asp ]
Viruses employed as construction workers to help build lithium-ion batteries and solar cells.

rsc.org

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From: donpat8/2/2006 2:24:28 PM
   of 12865
 
Mayo Clinic researchers make anti-cancer virus discovery

1st August 2006
By Helen Marshall

Mayo Clinic researchers, working with colleagues in Germany, claim to have devised a multi-level safety feature for therapeutic viruses used to treat cancer.

In the process of making cancer-killing viruses more specific to cancer tumor cells, they report having improved the therapeutic effectiveness of viruses. They did this by engineering a modified measles virus that turns on only in the presence of secretions specific to malignant cancer cells.

The investigation was performed in laboratory mice that were transplanted with a human cancer. The process is still experimental - and thus, years away from clinical use in humans. However, the Mayo results may be immediately useful in designing improved cancer treatments for humans, the researchers believe.

"Our work shows that oncolytic measles virus particle activation can be made dependent on substances secreted by cancer cells, and this enhances safety," explained Dr Roberto Cattaneo, lead researcher on the Mayo team. "By doing this, our study broadens the safeguarding strategies possible to tightly restrict the targeted virus to cancer cells."

The researchers say their contribution is a key advance because it provides a method of designing a therapeutic virus that is safe, stable and that reliably targets and kills cancer cells. Importantly, it appears to greatly reduce the possibility that the virus would erroneously turn on and harm the patient by causing unintended infection.

As such, the Mayo innovation of the cancer-activated virus could represent a helpful safety advance for the promising experimental field of 'oncolytic virotherapy.'

pharmaceutical-business-review.com

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To: donpat who wrote (1342)8/7/2006 8:51:36 AM
From: xcentral1
   of 12865
 
NanoViricides Addresses Shareholders' Questions Regarding Price per Share

WEST HAVEN, Conn., Aug 07, 2006 (BUSINESS WIRE) -- NanoViricides, Inc. (Pink Sheets:NNVC) recently requested that shareholders email the Company with questions and suggestions. Many shareholders have requested that management discuss the important issue of "price per share".
The Company's products and technologies address two important markets that are highly desired by institutional investors, Biopharma and Nanotechnology. NanoViricides believes it is now the very first company to bring a robust nanotechnology approach to antiviral medicines. "To develop nanomedicines that would be able to circulate in the body, seeking the pathogen, attacking and then destroying it. These new physical entities would be smaller than many viruses and almost a thousand times thinner than the width of a human hair. That was the intention of the inventor of our technology, Dr. Anil Diwan, when he started working on this project thirteen years ago," said Eugene Seymour, MD, MPH, Chief Executive Officer.

He continued, "We believe we have the fastest growing and most robust drug development pipeline for a startup company in the pharmaceutical industry today. In our first year of operation, we have advanced three drugs into preclinical animal studies, with more to follow. We have accomplished so much in this first year that it would be hard to find a similar biopharma/nanotechnology company that has achieved so much in such a short period of time."

"The Company's core nanotechnology science addresses a number of very large viral disease markets," Mr. Leo Ehrlich, CFO, commented, "Management understands the importance of capital markets and its stockholders interest in value through a rising stock price. We will strive to make NanoViricides a part of industry specific indexes and fund holdings once we complete our SEC filing which is necessary to become a fully reporting company."

In March, San Francisco-based Global Crown Capital LLC announced the launch of the industry's first pure play nanotechnology index that represents the emerging nanotechnology industry which includes nanomedicine.

Other nanotechnology investment funds include, Harris and Harris (TINY), Punk Ziegel Nanotech Index, the Merrill Lynch Nanotech Index, the Lux Nanotech Index(TM), PowerShares Lux Nanotech Portfolio, and the Innovest Strategic Value Advisors Nanotech Index.

This release is part of management's desire to better communicate with its shareholders about its science and technology as it prepares to file with the SEC. The SEC filing, presently being prepared, will contain important information which clearly explains NanoViricides' accomplishments to date, the technology, its financials and the associated risk factors.

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From: donpat8/7/2006 9:28:36 AM
   of 12865
 
NanoVic award for targeted drug delivery PhD research

8/5/2006 1:47:17 PM

Targeted drug delivery has the potential to greatly improve the therapeutic effect of existing drugs by delivering high doses of a drug to the specific sites where it is required.

The NanoVic award, to Ms Christina Cortez in the University’s Centre for Nano-science and Nanotechnology (CNST), is worth $4000 including a day’s access to commercialisation experts to discuss plans to implement research outcomes.

Ms Cortez is investigating the ‘biofunctionalisation’ of drug-loadable polymer particles and capsules coated with specific monoclonal antibodies to target colorectal cancer cells.

Her work is supervised by nanotechnology pioneer and Australian Research Council Federation Fellow Professor Frank Caruso, Director of the CNST, which is based in the University’s Department of Chemical and Biomolecular Engineering.

Ms Cortez’s project builds on a multidisciplinary body of nanobiotechnology research conducted in collaboration with researchers at the Ludwig Institute for Cancer Research in Parkville.

She says various nano- and microparticle-based delivery systems are being investigated, small size and drug-loading capability being among key criteria.

“The particles we work with at the CNST are prepared using a layer-by-layer (LbL) approach, where a polymer film of nano-sized thickness is assembled by depositing alternatively charged species on a particle template or core. The core can then be decomposed to form hollow capsules with high loading capabilities,” she says. Professor Caruso is a pioneer of the LbL method of capsule preparation.

Ms Cortez’s findings indicate that LbL nanocapsules biofunctionalised with a monoclonal antibody called huA33 mAb have the potential to target colorectal cancer cells with high specificity, considerably reducing unwanted drug toxicity effects on other tissues or cells.

Her work was recently accepted for publication by the high ranking journal Advanced Materials.

The next step of her project will see Ms Cortez undertake work in Strasbourg, France, on a collaborative research visit funded by the Australian Research Council Nanotechnology Network and the University through the Department of Chemical and Biomolecular Engineering and the Particulate Fluids Processing Centre. While in Strasbourg, Ms Cortez will examine the use of biocompatible and biodegradable polymers for preparing capsules.

Ms Cortez’s award was one of three made this year to doctoral candidates at Victorian universities and the second made to a CNST PhD student – Ms Alexandra Angelatos having won a NanoVic award last year for work relating to the release of therapeutics from microcapsules using electromagnetic radiation.
nanotechwire.com

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From: donpat8/7/2006 7:48:35 PM
   of 12865
 
October: Avian flu vaccines to be tested on humans

Updated on 8/7/2006 at 16:47

If nothing changes, avian flu vaccines will be tested on humans this October, said the Central Institute of Epidemiology.

The vaccines will firstly be tested on 30 people and after that 100 volunteers. The institute is now completing procedures and legal files for the test.

Moreover, in Khanh Hoa province, the Nha Trang national institute for vaccine and biological product production said that it was successful in testing anti-H5N1 vaccines in chickens and mice.

These vaccines will be brought to Hanoi for further quality testing by the Ministry of Health.

The Ministry of Agriculture and Rural Development has sent 4 working delegations from the Veterinary Department to hot areas to prevent recurrences of the disease.

The delegations are focusing on sanitising the environment, checking the vaccination of poultry, and inspecting the trading and slaughtering of poultry at domestic markets and border areas.

cpv.org.vn

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To: donpat who wrote (1345)8/7/2006 7:53:14 PM
From: donpat
   of 12865
 
Diwan has stated that a vaccine was a possible outgrowth of the nanoviricide development. Makes one wonder if NNVC is involved in whatever way in this avian flu vaccine.

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To: donpat who wrote (1346)8/8/2006 8:28:47 AM
From: xcentral1
   of 12865
 
The news is coming out of Vietnam...
I would think that this is part of their effort .... NNVC, hired by the Vietnam Gov't to tackle the problem and to that end - was supplied w/live biomaterial....

Kewel!!!!!

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From: donpat8/8/2006 9:15:18 AM
   of 12865
 
RNA Interference In Vitro and In Vivo Using a Novel Chitosan/siRNA Nanoparticle System

An exciting area in anticancer drug development involves using small interfering RNA (siRNA) molecules to reduce the levels of key proteins involved in the development of malignant cells. Naked RNA molecules are not stable in the bloodstream, however, so researchers are searching for effective methods of delivering intact, functional siRNA agents into tumor cells. Now, work from the University of Aarhus, in Denmark, shows that nanoparticles may serve as suitable delivery vehicles for siRNA.

Writing in the journal Molecular Therapy, a team of researchers headed by Jørgen Kjems, Ph.D., describes its use of the sugar-based polymer chitosan to form self-assembling nanoparticles that entrap siRNA molecules. These nanoparticles, which are stabilized by strong intermolecular interactions between chitosan and negatively charged RNA molecules, are taken up rapidly by tumor cells grown in culture. More importantly, the investigators found that these nanoparticles successfully delivered siRNA molecules into the cytoplasm of the cultured cells, and as a result, reduced production of a key tumor-associated protein by 90 percent.

Based on these successful in vitro tests, the investigators then administered chitosan-siRNA nanoparticles to mice that had been engineered to produce green fluorescent protein in lung cells. The nanoparticles, which were administered through the nose in order to reduce clearance by the immune system, successfully reduced green fluorescent protein synthesis by up to 43 percent in live animals. The researchers note that they are now developing a second generation chitosan-based nanoparticle that they will be able to deliver using a nebulizer.

This work is detailed in a publication titled, “RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed. View abstract.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16829204&query_hl=11&itool=pubmed_docsum ]

nano.cancer.gov

Posted 8th August 2006
azonano.com

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To: donpat who wrote (1348)8/10/2006 12:25:51 PM
From: xcentral1
   of 12865
 
NNVC --
NanoViricides Scheduled to Test Rabies Drug; Company on Course to Develop More Drugs Against Additional Diseases

WEST HAVEN, Conn., Aug 10, 2006 (BUSINESS WIRE) -- NanoViricides, Inc. (Pink Sheets:NNVC) announced today that the Company's latest drug, RabiCide(TM)-I, an anti-rabies drug, is now scheduled to begin preclinical animal testing in Vietnam by early 2007. Although not an important disease in the United States, rabies kills over 50,000 people per year in the subtropical regions of Asia, India and Africa. This drug was developed at the request of the National Institute of Hygiene and Epidemiology of the Ministry of Health, Government of Vietnam.
According to Eugene Seymour, MD, MPH, Chief Executive Officer, "The World Health Organization (WHO) reports that more than 10 million people receive post-exposure vaccination against this disease. Thus the size of the potential market for our drug is larger than anyone at first suspected. The timing of this testing is quite fortuitous since the Chinese government has destroyed 50,000 dogs and may kill as many as 500,000 more in an effort to stop this evolving rabies epidemic in the Yunnan Province according to online reports and a front page article in The Wall Street Journal of August 8th."

"It has taken us a very short time to design and develop a drug against rabies, following our success with general Influenza (FluCide(TM)-I) and H5N1 (AviFluCide(TM)-I). This is because we simply had to swap the ligand that encodes the address of the virus to the core nanomaterial that is the viricide's engine," said Anil R. Diwan, Ph.D. President. "Our success in quickly developing Rabicide-I now makes us confident that we can develop a drug against almost any viral disease, soon after we perform R&D to develop a good ligand that binds to the virus. Of course, the efficacy of each drug can only be determined experimentally."

"NanoViricides is on course to develop more drugs against additional diseases in due course. We believe that our drug pipeline is not only rich, robust, and expanding rapidly, but that it will continue to expand for several years into the future as additional applications of nanoviricides technology continue to evolve," added Dr. Eugene Seymour, the Company's CEO.

About NanoViricides - nanoviricides.com

NanoViricides, Inc. is a development stage company that is creating special purpose nanomaterials for viral therapy. A NanoViricide(TM) is a specially designed, flexible, nanomaterial that contains an encapsulated active pharmaceutical ingredient and targets it to a specific type of virus, like a guided missile. NanoViricide drugs are designed to block and dismantle the virus particles before they can infect a cell, thereby controlling viremia. This is a completely novel approach that is proving to be superior to existing approaches. This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Forward-looking statements involve risks and uncertainties. Actual events could differ materially and substantially from those projected herein and depend on a number of factors including the success of the Company's research and development strategy, the availability of adequate financing, the successful and timely completion of clinical studies and the uncertainties related to the regulatory process.

SOURCE: NanoViricides, Inc.

CONTACT: NanoViricides, Inc.
Leo Ehrlich, 917-853-6440
leo@nanoviricides.com

Copyright Business Wire 2006

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