NASA SBIR 2004 Solicitation


PROPOSAL NUMBER: 04 S4.05-9901
SUBTOPIC TITLE: Astrobiology
PROPOSAL TITLE: Single Molecule Scanning of DNA Radiation Oxidative Damage

SMALL BUSINESS CONCERN (Name, E-mail, Mail Address, City/State/Zip, Phone)
The DNA Medicine Institute
116 Charles Street, Suite 6
Boston, MA 02114-3217

PRINCIPAL INVESTIGATOR/PROJECT MANAGER (Name, E-mail, Mail Address, City/State/Zip, Phone)
Eugene Chan
116 Charles Street, Suite 6
Boston, MA 02114-3217

This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure; this will result in a highly quantitative approach to real-time health monitoring, dose response studies, studies of cancer progression, and systematic analyses of immunologically compromised cells. Exposure to radiation damages DNA. Reactive oxygen species (ROS) are liberated, causing oxidative damage to DNA bases. The major consequence of this damage is misincorporation of bases during replication, leading to irreversible cell damage, cancer or compromised cell function.

Oxidatively damaged genomic DNA is tagged at the lesions using specific antibodies, and the resultant DNA is scanned in a linear manner by our single molecule nanodevice. The locations, amount, and type of lesions are recorded for each DNA molecule. Megabase pair DNA is scanned by the reader in milliseconds, at ultra-sensitive single molecule detection limits. The technology is highly practical based on our significant experiences in developing single molecule scanning technologies. The potential nanoscale device and analysis speed create new possibilities for routine implementation. This addresses a current unmet need since there are no existing technologies that allow comprehensive assessment of DNA oxidative damage.

Space radiation poses significant risks for human travel across the solar system. Substantial new research and technology for understanding the susceptibility and sensitivity to solid cancer, immunological damage risks, and other health risks are required. First, without adequate study of radiation effects to determine minimal thresholds for early detection of damaged cells, humans may be exposed to toxic levels of radiation without knowing it. Second, the development of our assay allows the real-time measurement and monitoring of levels of DNA damage during space flight. Third, new therapies that correct oxidative damage can be developed with a highly sensitive assay.

Drugs, environmental insults, and chemotherapy can oxidatively damage DNA, leading to irreversible DNA lesions. The effects of DNA damage are cumulative, since cancer and other disorders require multiple genetic defects prior to manifestation. First, there is significant opportunity for early disease detection, offering possibilities for timely intervention. Second, the existence of our proposed assay offers a new platform for drug companies to develop approaches to reverse oxidative damage, potentially through the upregulation of DNA repair enzymes, such as the enzyme OGG, which has a major role in the prevention of reactive oxygen species-induced carcinogenesis.