Title:  Use of locally applied DNA fragments

United States Patent:  6,147,056

Assignee:  Trustees of Boston University (Boston, MA)

Filed:  March 26, 1998

Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, vitiligo, atopic dermatitis, or hyperproliferative or UV-responsive dermatoses, hyperproliferative or allergically mediated diseases of other epithelia and methods for reducing photoaging or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are disclosed.

SUMMARY OF THE INVENTION

The present invention pertains to repair for any type of DNA damage, in whole or in part, by induction of DNA repair mechanisms such as nucleotide excision repair. The DNA damage can be caused by ultraviolet irradiation, or by exposure to DNA-damage inducing chemicals or carcinogens, such as benzo(a)pyrene (BP).

The current invention further pertains to methods of treating or preventing hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis or other skin diseases, including contact dermatitis and other hyperproliferative, pre-cancerous or UV-responsive dermatoses, in a mammal. The invention further comprises methods of prophylaxis against skin cancer or reduction in the likelihood of development of skin cancer, as well as reduction of severity of photoaging resulting from sun exposure, in a mammal, including humans. The methods comprise contacting cells (or introducing into cells) of a mammal with single-stranded DNA fragments, (e.g., oligonucleotides or polynucleotides) deoxynucleotides, dinucleotides, dinucleotide dimers or a mixture thereof, such that the DNA fragments, deoxynucleotides, dinucleotides, or dinucleotide dimers are available to the cells. Alternatively, cells are contacted with an agent that increases the activity of p53 protein and therefore stimulates nucleotide excision repair. The fragments, deoxynucleotides or dinucleotides, or agent that increase p53 activity resulting in an increase in nucleotide excision repair, can be introduced topically, orally, by aerosol, or by any other appropriate means, such as by instillation. The DNA fragments, or deoxynucleotides or dinucleotides can be ultraviolet-irradiated.

The invention also includes compositions useful in the above methods, comprising DNA fragments, deoxynucleotides, dinucleotides or dinucleotide dimers, or an agent that increases p53 activity and thus increases nucleotide excision repair, in an appropriate delivery vehicle, such as liposomes.

Claim 1 of 5 Claims

What is claimed is:

1. A method of treating psoriasis in a mammal, comprising administering topically to the epidermis of the mammal an effective amount of DNA fragments selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 2 SEQ ID NO: 3 and SEQ ID NO: 4 and combinations thereof.

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