Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Patent
1992-08-17
1994-04-12
Wax, Robert A.
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
424 943, 424450, A61K 3722, A61K 3754
Patent
active
053023897
ABSTRACT:
Exposing the skin to UV radiation interferes with the induction of the T-cell mediated immune response, including both delayed (DHS) and contact (CHS) hyper-sensitivity immune responses initiated at non-irradiated sites. The present inventors have discovered that DNA is at least one of the targets for UV-induced hypersensitivity, and demonstrate that the application of DNA repair enzymes can reverse the damaging effects of UV irradiation on both the DHS and CHS response. The usefulness of the invention in this regard was tested using a model immunosuppression system in mice. In these studies, mice were first exposed to UV radiation and then liposomes were used to deliver a dimer-specific excision repair enzyme to their epidermis in situ. The application of liposomal T4 endonuclease V encapsulated to the UV-irradiated skin both decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. These studies illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage, including preventing or reversing viral activation (e.g., herpes virus activation), oncogene expression, or autoimmune episodes.
REFERENCES:
patent: 4959205 (1990-09-01), Brunner et al.
patent: 5077211 (1991-12-01), Yarosh
Kripke, M. L. et al., "Effect of T4N5 Liposome-Enhanced DNA Repair on UV-Induced Immune Suppression in the Mouse," S/pm-D6, Photochemistry & Photobiology, 53:Suppl., Apr. 1991, p. 295.
Yarosh, D. B. et al., "T4N5 Liposomes Reduce UV Mutagenesis in Mammalian Cells by Increasing Dimer Repiar and Reducing the Patch Size," S/pm-D7, Photochemistry & Photobiology, 53:Suppl., Apr. 1991, p. 295.
Kripke, M. L. et al.; Proc. Natl. Acad. Sci. USA 89:7516-7520 (Aug. 15, 1992).
Kripke, M. L. et al.; J. Invest. Dermatol. 86:543-549 (1986).
Applegate, L. A. et al.: Identification of the Molecular Target for the Suppression of Contact Hypersensitivity by Ultraviolet Radiation. J. Exp. Med. 170:1117-1131 (1989).
Yarosh, D. et al.: Pyrimidine Dimer Removal Enhanced by DNA Repair Liposomes Reduces the Incidence of UV Skin Cancer in Mice, Cancer Research 52:4227-4231 (Aug. 1, 1992).
Kripke Margaret L.
Yarosh Daniel B.
Board of Regents , The University of Texas System
Grimes Eric
Wax Robert A.
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