Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computer-designed protein triggers self-destruction of Epstein-Barr-infected cancer cells

20.06.2014

Delivered to its intracellular target via a novel carrier, 'BINDI' suppresses tumor growth and extends survival in a lab model of lymphoma

A protein molecule, "BINDI," has been built to trigger self-destruction of cancer cells infected with the Epstein-Barr virus. Numerous cancers are linked to the Epstein-Barr virus, which can disrupt the body's weeding of old, abnormal, infected and damaged cells.


A small chunk of protein (red) bound to the Epstein-Barr virus target protein (gray) was extended to make a much longer protein, left, and then designed to have a rigid folded structure, right, for tight and specific interactions with the target.

Credit: UW Molecular Engineering and Sciences Institute

The Epstein-Barr virus persists for a long time after a bout with mononucleosis or other diseases for which it is responsible. It survives by preventing cells from disintegrating to kill themselves and their invaders. The virus' interference with cell population control may contribute to cancerous overgrowth.

In a June 19 report in the scientific journal Cell, researchers describe how they computer-designed, engineered and tested a protein that overrides the virus' interference. BINDI, they discovered, can prompt Epstein-Barr-infected cancer cell lines to shrivel, disassemble their components and burst into small pieces.

The BINDI protein was created at the UW Institute for Protein Design. (BINDI is an acronym for BHRF1-INhibiting Design acting Intracellularly.)

Lead authors of the paper are Erik Procko of the Department of Biochemistry and Geoffrey Y. Berguig of the Department of Bioengineering, both at the University of Washington. They collaborated with scientists and clinicians at the UW, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance and Scripps Research Institute.

The research team also tested the protein in a laboratory model of Epstein-Barr virus-positive lymphoma. Lymphoma is a type of cancer that can affect the lymph nodes, spleen, bone marrow, blood and other areas of the body. The researchers grafted lymphoma tissue onto mice as a living system to evaluate BINDI's therapeutic properties.

The scientists delivered the protein into cancer cells via an antibody-targeted nanocarrier newly designed to deliver protein cargo to intracellular cancer targets. BINDI behaved as ordered: It suppressed tumor growth and enabled the mice to live longer.

"We are especially interested in designing proteins that selectively kill targeted cells," the researchers noted, "because they may provide advantages over current compounds that are toxic to other cells."

The work also demonstrates the potential to develop new classes of intracellular protein drugs, as current protein therapeutics are limited to extracellular targets.

BINDI was designed to recognize and attach itself to an Epstein-Barr virus protein called BHRF1, and to ignore similar proteins. BHRF1 keeps cancer cells alive, but when bound to BINDI, it can no longer fend off cell death.

By examining the crystal structure of BINDI, the scientists saw that it nearly matched their computationally designed architecture for the protein molecule.

"This close agreement between the protein model and the actual structure highlights the success in which designer toxins can be developed," the researchers said.

Among the scientists on this project:

  • William Schief, noted for his new approaches to vaccine development;
  • Oliver Press, a Hutchinson cancer center oncologist who studies and treats lymphoma and related disorders;
  • David M. Hockenbery, whose lab at Fred Hutchinson explores the mechanisms of programmed cell death;
  • Barry L. Stoddard, also at Fred Hutchinson, who is engineering therapeutic enzymes;
  • Patrick S. Stayton, a UW bioengineering professor and director of the UW Molecular Engineering and Science Institute, who works on new drug delivery systems;
  • David Baker, a UW biochemistry professor and director of the UW Institute for Protein Design, who has pioneered the computational design of proteins.

Grants from the National Institute of General Medical Studies at the National Institutes of Health (P41 GM103533, R01 GM49857, R21EB014572), Washington Life Sciences Discovery Fund and the U.S. Defense Threat Reduction Agency supported this project. Computational resources came from Berkeley Open Infrastructure for Network Computing, which received National Science Foundation support.

Stayton and Press are co-founders of PhaseRx Pharmaceuticals, which holds licenses for aspects of the new drug delivery carrier tested in this study, but indicated that the work reported is independent of the firm.

Elizabeth Hunter | Eurek Alert!
Further information:
http://www.washington.edu

Further reports about: Epstein-Barr Hutchinson death lymphoma proteins structure

More articles from Life Sciences:

nachricht Cells migrate collectively by intermittent bursts of activity
30.09.2016 | Aalto University

nachricht The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>