Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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


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:

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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Reliable in-line inspections of high-strength automotive body parts within seconds

Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.

To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...

Im Focus: Kick-off for a new era of precision astronomy

The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.

As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...

Im Focus: Locusts at the wheel: University of Graz investigates collision detector inspired by insect eyes

Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.

Inspired by insects

Im Focus: Physicists shrink particle accelerator

Prototype demonstrates feasibility of building terahertz accelerators

An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...

Im Focus: Simple detection of magnetic skyrmions

New physical effect: researchers discover a change of electrical resistance in magnetic whirls

At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Unexpected information about Earth's climate history from Yellow River sediment

09.10.2015 | Earth Sciences

Single atom alloy platinum-copper catalysts cut costs, boost green technology

09.10.2015 | Life Sciences

Indefatigable Hearing

09.10.2015 | Life Sciences

More VideoLinks >>>