NIH Selects Purdue to use phi29 DNA Packaging Motor for National Nanomedicine Development Center

The National Institutes of Health awarded the Purdue research team $7 million over five years to study the use of a nanomotor, a microscopic biological machine, for potential use in the diagnosis and treatment of diseases such as cancer, AIDS, hepatitis B and influenza.

The team will take the first steps in research that could lead to using nanomotors to package and deliver therapeutic DNA or RNA to disease-causing cells.

This is a feat that could revolutionize medicine, but it faces many challenges, said Peixuan Guo, director of the center and a professor of molecular virology with joint appointments in Purdue's Cancer Research Center, School of Veterinary Medicine and Weldon School of Biomedical Engineering.

"Nanomedicine, a branch of nanotechnology, calls upon many fields, including engineering, biology, chemistry, mathematics, computation and physics," Guo said.

"The NIH centers bring these scientists together and that is the most exciting aspect of this project. We hope to create a medical tool using a device that mimics a natural biological structure. This biomimetic tool will be a hybrid of natural biological structures and synthetic structures that will operate on the nanoscale."

Nanotechnology is defined as structures, devices and systems 1 to 100 nanometers in size that possess novel properties and functions due to the arrangement of their atoms and molecules. A nanometer is one-billionth of a meter, or 100,000 times smaller than the diameter of a human hair.

The NIH nanomedicine initiative is a network of centers studying biological systems at the nanoscale in an effort to understand and control the molecular complexes responsible for cellular processes.

The long-term goal is to develop devices that can control these processes for diagnosis and treatment of diseases. Four nanomedicine centers were funded last year, and the NIH recently announced the final four centers.

The center's research will be the first to take advantage of the bio-pharma cleanroom resources of the new $10 million Scifres Nanofabrication Laboratory. This cleanroom offers a precisely controlled environment necessary for creation of nano-biotechnology devices.

Scientists worldwide have been trying for more than two decades to solve the problem of developing a delivery method that protects fragile deoxyribonucleic acid (DNA) and does not cause an adverse reaction in the patient.

Guo's nanomotor is derived from the biological motor of bacteriophage phi29, a virus that infects bacteria. The virus uses the motor to package DNA and move it into the capsid, a shell made of proteins, as part of the viral reproduction process.

The viral motor is geared by six packaging ribonucleic acid (pRNA) molecules arranged in a ring. Adenosine triphosphate (ATP), the same biological energy used for muscle movement, fuels the RNA motor. The DNA is cranked through the center of the RNA ring and into the capsid like a screw through a bolt.

Guo discovered this pRNA in 1987, and his research was published in the journal Science. In 1986 he was able to achieve a functional phi29-imitating nanomotor in a cell-free system, and his research was published in the Proceedings of the National Academy of Sciences.

The team now will work to use the nanomotor to package DNA in the same way, but move it into and out of a therapeutic delivery vehicle.

Guo and his team constructed the DNA-packaging systems of the nanomotors to contain modified synthetic pRNA and re-engineered protein molecules. The nanomotors retain the modified and re-engineered viral components, which are harmless to human cells because the phi29 bacteriophage only infects bacteria.

The modified nanomotors have the additional advantage of lowering the chance of an adverse immunologic response in a patient.

Other nanomedicine centers are located at Baylor College of Medicine University of Illinois, University of California at San Francisco, Columbia University, Georgia Institute of Technology, University of California at Los Angeles and the University of Calfornia Lawrence Berkeley National Laboratory.