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 How Plants isolate themselves against Bacteria
29.05.2015 | Julius-Maximilians-Universität Würzburg

nachricht How Plants become Carnivores
29.05.2015 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Lasers are the key to mastering challenges in lightweight construction

Many joining and cutting processes are possible only with lasers. New technologies make it possible to manufacture metal components with hollow structures that are significantly lighter and yet just as stable as solid components. In addition, lasers can be used to combine various lightweight construction materials and steels with each other. The Fraunhofer Institute for Laser Technology ILT in Aachen is presenting a range of such solutions at the LASER World of Photonics trade fair from June 22 to 25, 2015 in Munich, Germany, (Hall A3, Stand 121).

Lightweight construction materials are popular: aluminum is used in the bodywork of cars, for example, and aircraft fuselages already consist in large part of...

Im Focus: Solid-state photonics goes extreme ultraviolet

Using ultrashort laser pulses, scientists in Max Planck Institute of Quantum Optics have demonstrated the emission of extreme ultraviolet radiation from thin dielectric films and have investigated the underlying mechanisms.

In 1961, only shortly after the invention of the first laser, scientists exposed silicon dioxide crystals (also known as quartz) to an intense ruby laser to...

Im Focus: Advance in regenerative medicine

The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.

Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...

Im Focus: Basel Physicists Develop Efficient Method of Signal Transmission from Nanocomponents

Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.

Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...

Im Focus: IoT-based Advanced Automobile Parking Navigation System

Development and implementation of an advanced automobile parking navigation platform for parking services

To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International symposium: trends in spatial analysis and modelling for a more sustainable land use

20.05.2015 | Event News

15th conference of the International Association of Colloid and Interface Scientists

18.05.2015 | Event News

EHFG 2015: Securing health in Europe. Balancing priorities, sharing responsibilities

12.05.2015 | Event News

 
Latest News

How Plants become Carnivores

29.05.2015 | Life Sciences

Portable finger-probe device can successfully measure liver function in potential organ donors

29.05.2015 | Health and Medicine

Physicists precisely measure interaction between atoms and carbon surfaces

29.05.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>