University of Florida researchers develop nanorobot to target Hepatitis C...

Posted 7/16/12 on the University of Florida website. Nanotechnology represents a fascinating, potentially less lethal and more efficacious way to treat disease states without the side-effects common with oral and injectable drugs. Using Nanotechnology, University of Florida researchers have designed a nanozyme that hyper-targets the Hepatitis C virus. Using a two pronged attack - a DNA oligonucleotide that recognizes the genetic material to be destroyed and instructs it's partnered enzyme to destroy the virus' mRNA. Should it become feasible, we may have a hyper-targeted therapy to treat Hepatitis C that would avoid the majority of adverse events and side effects we see with traditional medicinal oral and injectable therapies. 


UF researchers develop “nanorobot” that can be programmed to target different diseases

Monday, July 16, 2012.

GAINESVILLE, Fla. — University of Florida researchers have moved a step closer to treating diseases on a cellular level by creating a tiny particle that can be programmed to shut down the genetic production line that cranks out disease-related proteins.

In laboratory tests, these newly created “nanorobots” all but eradicated hepatitis C virus infection. The programmable nature of the particle makes it potentially useful against diseases such as cancer and other viral infections.

The research effort, led by Y. Charles Cao, a UF associate professor of chemistry, and Dr. Chen Liu, a professor of pathology and endowed chair in gastrointestinal and liver research in the UF College of Medicine, is described online this week in the Proceedings of the National Academy of Sciences.

“This is a novel technology that may have broad application because it can target essentially any gene we want,” Liu said. “This opens the door to new fields so we can test many other things. We’re excited about it.”

During the past five decades, nanoparticles — particles so small that tens of thousands of them can fit on the head of a pin — have emerged as a viable foundation for new ways to diagnose, monitor and treat disease. Nanoparticle-based technologies are already in use in medical settings, such as in genetic testing and for pinpointing genetic markers of disease. And several related therapies are at varying stages of clinical trial.

The Holy Grail of nanotherapy is an agent so exquisitely selective that it enters only diseased cells, targets only the specified disease process within those cells and leaves healthy cells unharmed.

To demonstrate how this can work, Cao and colleagues, with funding from the National Institutes of Health, the Office of Naval Research and the UF Research Opportunity Seed Fund, created and tested a particle that targets hepatitis C virus in the liver and prevents the virus from making copies of itself.

Hepatitis C infection causes liver inflammation, which can eventually lead to scarring and cirrhosis. The disease is transmitted via contact with infected blood, most commonly through injection drug use, needlestick injuries in medical settings, and birth to an infected mother. More than 3 million people in the United States are infected and about 17,000 new cases are diagnosed each year, according to the Centers for Disease Control and Prevention. Patients can go many years without symptoms, which can include nausea, fatigue and abdominal discomfort.

Current hepatitis C treatments involve the use of drugs that attack the replication machinery of the virus. But the therapies are only partially effective, on average helping less than 50 percent of patients, according to studiespublished in The New England Journal of Medicine and other journals. Side effects vary widely from one medication to another, and can include flu-like symptoms, anemia and anxiety.

Cao and colleagues, including graduate student Soon Hye Yang and postdoctoral associates Zhongliang Wang, Hongyan Liu and Tie Wang, wanted to improve on the concept of interfering with the viral genetic material in a way that boosted therapy effectiveness and reduced side effects.

The particle they created can be tailored to match the genetic material of the desired target of attack, and to sneak into cells unnoticed by the body’s innate defense mechanisms.

Recognition of genetic material from potentially harmful sources is the basis of important treatments for a number of diseases, including cancer, that are linked to the production of detrimental proteins. It also has potential for use in detecting and destroying viruses used as bioweapons.

The new virus-destroyer, called a nanozyme, has a backbone of tiny gold particles and a surface with two main biological components. The first biological portion is a type of protein called an enzyme that can destroy the genetic recipe-carrier, called mRNA, for making the disease-related protein in question. The other component is a large molecule called a DNA oligonucleotide that recognizes the genetic material of the target to be destroyed and instructs its neighbor, the enzyme, to carry out the deed. By itself, the enzyme does not selectively attack hepatitis C, but the combo does the trick.

“They completely change their properties,” Cao said.

In laboratory tests, the treatment led to almost a 100 percent decrease in hepatitis C virus levels. In addition, it did not trigger the body’s defense mechanism, and that reduced the chance of side effects. Still, additional testing is needed to determine the safety of the approach.

Future therapies could potentially be in pill form.

“We can effectively stop hepatitis C infection if this technology can be further developed for clinical use,” said Liu, who is a member of The UF Shands Cancer Center.
The UF nanoparticle design takes inspiration from the Nobel prize-winning discovery of a process in the body in which one part of a two-component complex destroys the genetic instructions for manufacturing protein, and the other part serves to hold off the body’s immune system attacks. This complex controls many naturally occurring processes in the body, so drugs that imitate it have the potential to hijack the production of proteins needed for normal function. The UF-developed therapy tricks the body into accepting it as part of the normal processes, but does not interfere with those processes.

“They’ve developed a nanoparticle that mimics a complex biological machine — that’s quite a powerful thing,” said nanoparticle expert Dr. C. Shad Thaxton, an assistant professor of urology at the Feinberg School of Medicine at Northwestern University and co-founder of the biotechnology company AuraSense LLC, who was not involved in the UF study. “The promise of nanotechnology is extraordinary. It will have a real and significant impact on how we practice medicine.”

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Santaris Pharma A/S provides update on Miravirsen for treatment of HCV...

Santaris Pharma A/S gives a preview update on miravirsen for treatment of HCV that will be presented at the 7th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held September 8-10 in Copenhagen, Denmark. Miravirsen is the first microRNA-targeted drug inhibiting miR-122 to make it to clinic (it's currently in phase II trials) and to specifically target HCV. Miravirsen is the result of Santaris Pharma A/S propritary Locked Nucleic Acid Technology (LNA)drug platform, which has the potential to deliver drugs 'naked' without the complex delivery systems of RNA-based drugs. LNA-based compounds have the potential to inhibit entire microRNA families and is a new approach that opens up possibilities of successfully treating complex diseases such as cancer, viral infections, cardiovascular and muscle diseases

Santaris Pharma A/S Showcases microRNA and mRNA Research Advancements Utilizing its Proprietary Locked Nucleic Acid Technology at Oligonucleotide Therapeutics Society Meeting

HOERSHOLM, Denmark and SAN DIEGO, September 7, 2011 /PRNewswire/ --

Santaris Pharma A/S provides update on the development of miravirsen, a microRNA-targeted drug inhibiting miR-122, which is currently in Phase 2 clinical trials to treat patients infected with the Hepatitis C virus (HCV)
Scientists at Santaris Pharma A/S demonstrate specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating cancer, viral infections, cardiovascular and muscle diseases

Data presented by scientists at Santaris Pharma A/S demonstrate successful "naked" delivery uptake of LNA-based compounds, a key advantage over other RNA-based technologies that require complex delivery vehicles
Versatility of the LNA Drug Platform allows Santaris Pharma A/S to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties


Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, today announced advancements from the company's RNA-targeted research programs utilizing its proprietary Locked Nucleic Acid (LNA) Drug Platform. In addition to a presentation on the Company's microRNA-targeted drug miravirsen, a total of six abstracts/posters are being showcased at the 7th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held September 8-10 in Copenhagen, Denmark.

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates that can selectively inhibit mRNA and microRNA targets for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders.

"Santaris Pharma A/S is pleased to have the OTS hold its annual meeting here in Denmark this year as it recognizes the groundbreaking RNA-targeted research and development being conducted in Denmark from companies such as Santaris Pharma A/S as well as public institutions and research centers," said Henrik Oerum, Ph.D., Vice President and Chief Scientific Officer of Santaris Pharma A/S.

"Santaris Pharma A/S is excited to showcase its microRNA and mRNA-targeted research advancements utilizing its proprietary Locked Nucleic Acid Drug Platform," Dr. Oerum added. "The Company is providing an update on the progress of its lead microRNA-targeted drug candidate, miravirsen, for the treatment of Hepatitis C; presenting data on the use of Santaris Pharma A/S proprietary 'tiny' LNA-based drugs to inhibit entire microRNA-targeted families and highlighting data demonstrating 'naked' delivery uptake of LNA-based drugs, a key advantage over other RNA based technologies. This collection of data attests to the versatility of the LNA Drug Platform and clearly supports Santaris Pharma A/S leadership position in discovering and developing RNA-targeted medicines."

In a talk titled, "Targeting miRNA-122 for the Treatment of HCV," Dr. Oerum will provide an update on the development of miravirsen, the first microRNA-targeted drug to enter clinical trials, which is now in Phase 2 studies to assess the safety and tolerability of the drug in treatment-naïve patients infected with HCV. Data from Phase 1 clinical studies with miravirsen in healthy volunteers show that the drug is well tolerated.

Previously published data in Science demonstrated that miravirsen successfully inhibited miR-122 and dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus(1). Because of its unique mechanism of action and tolerability profile, miravirsen has the potential to be an effective treatment option for patients with HCV.

In addition, scientists at Santaris Pharma A/S will present data using proprietary bioinformatics techniques to demonstrate the specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating a range of diseases including cancer, viral infections, cardiovascular and muscle diseases. Recent data published in Nature Genetics showed that the high affinity and target specificity of tiny LNA-based compounds enabled functional inhibition of entire microRNA families in a range of tissues without off-target effects(2).

MicroRNAs have emerged as an important class of small regulatory RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression associated with many diseases. Because they dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets in the treatment of many disease processes.

Santaris Pharma A/S also will present data demonstrating successful "naked" delivery uptake of LNA-based compounds, an advantage over other RNA-based technologies that require complex delivery vehicles. Data showed that LNA-based compounds readily enter cells in an active form allowing in vitro prediction of potent therapeutically active compounds as well as in vivo distribution to manifold cell types and tissues. Without the need for using complex delivery vehicles, the versatility of the LNA Drug Platform is the key for scientists to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties.

The Santaris Pharma A/S LNA Drug Platform is the only RNA technology with both mRNA and microRNA targeted drugs in clinical trials, demonstrating the broad utility of the proprietary platform. In September 2010, Santaris Pharma A/S successfully advanced miravirsen, a lead microRNA drug candidate targeting miR-122, into Phase 2 studies for the treatment of patients infected with the Hepatitis C virus. In addition, Santaris Pharma A/S also advanced two mRNA-targeted drugs, SPC5001 targeting PCSK9 and SPC4955 targeting apoB, for the treatment of high cholesterol into Phase 1 in May 2011.

With its partners, Santaris Pharma A/S has a robust product pipeline consisting of mRNA and microRNA drug discovery and development collaborations. These include partnerships with Pfizer, Inc. (delivery of lead candidates against up to 20 targets), miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), GlaxoSmithKline (four viral disease drug candidates) and Enzon Pharmaceuticals (eight cancer targets successfully delivered - three are now in Phase 1 clinical studies).

About Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA-based drugs are a promising new class of therapeutics that are enabling scientists to develop drug candidates to target pathways previously considered inaccessible. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.

About Santaris Pharma A/S

Santaris Pharma A/S is a privately held clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The Company's research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies include a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The Company has strategic partnerships with miRagen Therapeutics, Shire plc, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the Company holds exclusive worldwide rights to all therapeutic uses of LNA. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit http://www.santaris.com for more information.

(1) Lanford et al, Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327 (5962): 198-201

(2) Obad, et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nature Genetics 10.1038/ng.786.