Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ribozyme package effective against hepatitis B virus

23.03.2004


Penn State College of Medicine researchers have developed a tiny package that searches for and destroys up to 80 percent of hepatitis B virus in the livers of mice.



"This marks one of the few successful in vivo, or in-animal, models of an effective therapy to reduce the production of hepatitis B virus," said Gary Clawson, M.D., Ph.D., professor of pathology, biochemistry and molecular biology, Penn State College of Medicine. "Although this work focused on hepatitis B virus, our method of targeting and packaging ribozymes should also be applicable to the development of therapies to fight other viruses."

The study was published March 5 in the online version of the journal, Molecular Therapy, the official journal of the American Society of Gene Therapy, and will appear in the journal’s April print edition.


Hepatitis B virus (HBV) attacks the liver and can cause lifelong infection, liver cancer and, eventually, death. Although HBV is treated with drugs, it cannot be cured. The chronic disease affects about 1.25 million Americans, 20 percent to 30 percent of whom acquired the virus in childhood. HBV is transmitted via blood or sexual activity, but also may be transmitted from mother to child during childbirth. Once infected, the virus continues to reproduce in the liver.

Clawson, who is also director of the Jake Gittlen Cancer Research Center at Penn State Milton S. Hershey Medical Center, and his team developed the SNIPAA cassette, which contains a double-dose of a special type of ribozyme called a trans-acting hammerhead ribozyme. Ribozymes are ribonucleic acid (RNA) segments that, like enzymes, cause chemical changes or splitting in other RNA segments. RNA, which is critical to the replication of DNA - life’s instruction book - also is critical to the replication of viruses. The SNIPAA cassette was packaged in liposomes, typical vehicles for delivering drugs in the body, and the liposomes in turn were modified with proteins so that they would seek out the liver cells where the HBVs replicate.

Once at the liver cell, the SNIPAA cassette package is released into the cell and finds its way to the cell nucleus, where the active ribozymes are produced. The ribozymes destroy the viral RNA’s ability to produce proteins by cleaving, or cutting, the viral RNAs, rendering them useless. Proteins are critical to virus replication.

First, Clawson and co-workers used proprietary in vitro selection techniques to identify the best target sites in HBV RNA, and then used cells in culture to test the effectiveness of the cassette. In the cell cultures, he found that the SNIPAA cassette containing a double-dose of ribozymes eliminated more of the virus over a period of three to five days than did cassettes containing a single dose of the ribozymes.

Specialized transgenic mice, which contain the HBV in their DNA and which are chronic carriers of HBV, were treated with the tiny HBV-fighting packages. Clawson and co-workers chose the dosage and schedule of the drug delivery to the mice based on their cell culture work. Studies with the transgenic mice were performed with John Morrey, Ph.D., at Utah State, under the auspices of an NIH contract which supports testing of antiviral reagents.

"The treatment effects were quite dramatic," Clawson said. "We recorded a greater than 80 percent reduction in the HBV liver DNA, meaning far less virus was being produced, and staining for the virus using antibodies also showed a dramatic decrease in residual viral production. This is significant because there are so few examples of successful in vivo applications of ribozymes against bona fide naturally-occurring, disease-causing organisms."

Clawson believes this cassette is more effective than previous ones for a number of reasons. First, the best target sites were chosen using a "library selection" process. Second, the ribozyme cassette is engineered to cut itself into pieces, thereby freeing the HBV-targeted ribozymes from extraneous sequences that could interfere with their activity. In addition, Clawson’s cassette included two distinct trans-acting ribozymes, whereas previous versions included only one. With two trans-acting hammerhead ribozymes in the SNIPAA cassette, twice the amount of "medicine" was present and was delivered over a longer period.


Co-authors on the study were: Wei-Hua Pan, Pin Xin, Departments of Pathology and Biochemistry and Molecular Biology, The Gittlen Cancer Research Institute, Penn State Milton S. Hershey Medical Center, and John D. Morrey, Institute for Antiviral Research, Utah State University.

This work was supported by a research and development contract with Biosan Laboratories/Hexal AG and by a contract from the National Institutes of Health.

Valerie Gliem | EurekAlert!
Further information:
http://www.psu.edu/

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>