Enhanced repair of ultraviolet light-damaged DNA by topical delivery of pyrimidine dimer glycosylases in phospholipid liposomes
OHSU # 1059
DNA REPAIR POLYPEPTIDES: A TREATMENT FOR UV INDUCED DNA DAMAGE
OHSU Technology 1059
Researchers at Oregon Health & Science University have discovered and developed novel natural and modified excision repair enzymes that can be topically applied to the skin for prophylactic and therapeutic treatment of ultraviolet light (UV) induced non-melanoma skin cancer, psoriasis, actinic keratosis, and UV-induced immunosuppression.
Sunlight exposure causes DNA damage in skin cells leads to the development of non-melanoma skin cancer. Human cells possess only one mechanism (Nucleotide Excision Repair, NER) for repair of ultraviolet light induced DNA damage. This mechanism is defective in individuals affected with Xeroderma Pigmentosum (XP) causing them to be ~2000-fold more cancer-prone than the general population. Human cells do have enzymes to complete another mechanism of DNA damage repair, Base Excision Repair (BER), but lack the specific pyrimidine dimer glycosylase (Pdg) needed to initiate BER in response to UV. The exogenous delivery of a photoproduct-specific Pdg protein to human skin has the potential to enhance DNA repair following UV exposure.
· 3.5 million basal cell and squamous cell carcinomas are diagnosed annually
· ~2000 people die each year from non-melanoma skin cancers
Amanda McCullough, Ph.D. is a Professor is an Associate Professor, Molecular and Medical Genetics, School of Medicine and a Scientist in the Center for Research on Occupational and Environmental Toxicology at Oregon Health & Science University. Dr. McCullough’s research interests are focused on the biochemical mechanisms of DNA repair systems and the regulation and roles of DNA repair in cellular responses to environmental stress.
R. Stephen Lloyd, Ph.D. is a Professor and Senior Scientist in the Center for Research on Occupational and Environmental Toxicology at Oregon Health & Science University. Dr Lloyd’s research interests are in DNA repair processes and high fidelity DNA replication represent the major mechanisms to maintain genomic stability, including strategies to prevent sunlight-induced skin cancer via the topical introduction of repair enzymes into human cells.
PATENT APPLICATIONS (OHSU Tech ID 1059):
International Application Number PCT/US2009/032710 filed and published
OHSU Technology 1059 is available for licensing or collaborative co-development.
Johnson, JL, Lowell, BC, Ryabinina, OP, Lloyd, RS, McCullough, AK. TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage, J Invest Dermatol. 131(3): 753-61, 2011.
- Stephen (Robert) Lloyd, CR.Center for Research on Occupational and Environmental Toxicology
- Amanda McCullough, CR.Center for Research on Occupational and Environmental Toxicology
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Technology Development Manager