Phi29 DNA-Packaging Motor for Nanomedicine

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Innovative biological machines, such as nanomotors and membrane channels, inspire the development of biomimetic devices that can provide the exquisite control of cellular processes for disease diagnostics and treatment. The phi29 is the strongest biomotor constructed to date. The motor is switchable, underscoring its highest efficiency in DNA insertion compared to all other in vitro viral packaging motors, making the motor a viable option as a mechanical component in nanotechnology applications. The long-term goal of the proposed Nanomotor Drug Delivery Center is to create biologically compatible membranes and arrays with embedded phi29 DMA-packaging motors for applications in medicine. This will be accomplished by focusing on three key areas of study: reverse engineering the phi29 motor; incorporating the active nanomotor into lipid bilayers; and developing active nanomotor arrays that enable drug delivery and diagnostics. The short-term goal of this center is to create liposomes and array structures with embedded phi29 DNA- packaging motors for both passive and active transport of DNA and drugs. The Center will develop hybrid systems that combine the best features of the biological nanomotor and synthetic delivery systems that have already achieved clinical acceptance. Initial efforts will provide engineering specifications for the structure and working mechanism of the phi29 nanomotorthat will enable us to produce engineered, hybrid, synthetic and functional nanomotors. Incorporation of active phi29 nanomotors in liposomes will be a major thrust that will enable nanoscale control for therapeutic approaches that have already gained acceptance in the clinic but still provide only blunt instruments for therapy of complex conditions such as cancer and infectious diseases. Additional team efforts will exploit our understanding of the reengineered membrane-addapted motor to create prototype nanomechanical devices for diagnostic applications, targeted delivery of therapeutics and for various nanomachines with application in medicine. These applications and the engineering principles underlying the physical action, energy transduction and transmembrane transport capabilities of the membrane adapted motors will be elucidated by our interdisciplinary team including physicists, chemists, engineers, mathematicians, physicians, and molecular biologists.