The Program of Excellence in Nanotechnology (PEN) for the treatment of Vulnerable Plaque is supported by a grant by the National Heart Lung and Blood Institute of the National Institutes of Health. This is a partnership of 25 scientists from The Burnham Institute, University of California Santa Barbara, and The Scripps Research Institute. The scientists are using $13 million award to design nanotechnologies to detect, monitor, treat, and eliminate ìvulnerableî plaque, the probable cause of death in sudden cardiac arrest.

Led by Jeffrey Smith, Ph.D., of the Burnham Institute and the principal investigator of the program, the scientific team is comprised of biochemists, vascular biologists, chemical engineers and physicists. "This is a novel approach to bring experts from all these fields together,î says Dr. Smith. ìAnd itís very exciting. These groups do not normally work together. But in this instance, I think itís going to produce some real scientific progress."

Recent studies have shown that plaque exists in two modes: stable and vulnerable. Blood passing through an artery exerts a sheering force and can cause the vulnerable plaque to rupture, which often leads to occlusion and myocardial infarction. This is a significant health issue as nearly one million people die each year from cardiac disease without showing any symptoms. As many as
sixty to eighty percent of sudden cardiac deaths can be attributed to the physical rupture of vulnerable plaque.

"We intend to exploit the synergy between the different scientific disciplines to devise nano-
devices, or molecular machines, that will specifically target and treat vulnerable plaque. That
cannot be accomplished today. My colleagues and I hope that our work will lead to real diagnostic and therapeutic strategies for those suffering from this form of cardiac disease."

"The Programs of Excellence in Nanotechnology is a vitally important research effort that will
spur the development of novel technologies to diagnose and treat heart, lung, and blood
diseases," said Elizabeth G. Nabel, M.D., director of the National Heart Lung and Blood Institute
of the NIH. "The program brings together bioengineers, materials scientists, biologists, and physicians who will work in interdisciplinary teams. By taking advantage of the unique properties
of materials at the nanoscale, these teams will devise creative solutions to medical problems."

PEN Director, Jeffrey Smith, Ph.D., Professor, The Burnham Institute, will oversee the Programís administrative and training components, as well as his own research component. Dr. Smith also directs the Center on Proteolytic Pathways at The Burnham Institute, recently established as one
of first centers funded by the National Institute of Healthís Roadmap Initiative. Erkki Ruoslahti,
M.D., Ph.D., Distinguished Scientist and former President/CEO of The Burnham Institute, using in vivo phage display technology discovered in his laboratory, will identify and develop targeting
elements needed to target the delivery of nanodevices to vulnerable plaque. Dr. Ruoslahti is credited with the first successful targeted delivery of a nanomachine into live tissue, using similar strategies. Also from The Burnham Institute are William B. Stallcup, Ph.D., Professor, and
Francesca Marassi, Ph.D., Assistant Professor, who will provide NMR expertise for structural
studies.

Zaverio M. Ruggeri, M.D., Professor, and a world-renowned expert in vascular pathology,
is collaborating from The Scripps Research Institute. The team from UC Santa Barbara will
contribute unique expertise in molecular engineering and nano-fabrication. They include
Matthew V. Tirrell, Ph.D., Dean of the College of Engineering and professor of chemical
engineering; Andrew Cleland, Ph.D., associate professor of physics; Patrick Daugherty, Ph.D., associate professor of chemical engineering; Samir Mitragotri, Ph.D., assistant professor of
chemical engineering; and Joseph Zasadzinski, Ph.D., professor of chemical engineering.

In concert with the NIHís strategy to accelerate progress in medical research through innovative technology and interdisciplinary research, cardiac disease was chosen as the focus of the
National Heart Lung and Blood Instituteís recently established Program of Excellence in Nanotechnology.