Therapeutic oligonucleotides targeting the human MDR1 and MRP genes
AssigneeBoard of Regents of the University of Nebraska
InventorLarry J. Smith
Life of this patent
Estimating the term…
Abstract
The present invention provides novel compositions and methods useful in cancer therapy for inhibiting the multidrug resistance phenotype, which often thwarts long-term chemotherapeutic regimens. The novel compositions of matter comprise oligonucleotides targeted to the human MDR1 and MRP genes, which inhibit expression of these genes, thereby rendering tumors and other forms of cancer more susceptible to the cytotoxic effects of chemotherapeutic agents. Oligonucleotides are also provided that inhibit the multidrug resistance phenotype by exerting an aptameric effect.
Claims32
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, having a sequence that specifically hybridizes in a human cell with a complementary sequence of a human MDR1 gene and allelic variants thereof to inhibit expression of a multidrug resistance phenotype exhibited by said cell, said complementary sequence being selected from the group consisting of Sequence ID Nos:
- 103, 104 and 105.
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, said oligonucleotide having a sequence that is fully complementary to and hybridizes with a sequence selected from the group consisting of Sequence ID Nos:
- 103, 104 and 105.
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, said oligonucleotide having a sequence that specifically hybridizes with a complementary sequence of the MDR1 gene and allelic variants thereof said oligonucleotide being selected from the group consisting of Sequence ID Nos:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 35, 36, 37, 38, 39, 40, 92, 93, 94, 95, 96, 97, 98, 99, 100 and 101.
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, consisting of a sequence that specifically hybridizes in a human cell with a complementary sequence of a human MRP gene and allelic variants thereof to inhibit expression of a multidrug resistance phenotype exhibited by said cell, said complementary sequence being selected from the group consisting of Sequence ID Nos:
- 106, 107, 108 and 109.
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, that is fully complementary to and hybridizes with a sequence selected from the group consisting of Sequence ID Nos:
- 106, 107, 108 and 109.
An oligonucleotide between 15 and 30 nucleotides in length, inclusive, that specifically hybridizes in a human cell with a complementary sequence of a MRP gene and allelic variants thereof selected from the group consisting of Sequence ID Nos:
- 42, 43, 44, 45, 46, 47, 48, 49, 60, 62, 64 and 76.
An oligonucleotide for inhibiting expression of the multidrug resistance phenotype, having a sequence selected from the group consisting of Sequence ID Nos:
- 5, 27, 28, 88, 89, 90 and 91.
An oligonucleotide between 17 and 30 nucleotides in length, inclusive, having a sequence that specifically hybridizes in a human cell with a complementary sequence of a human MDR1 gene and allelic variants thereof to inhibit expression of a multidrug resistance phenotype exhibited by said cell, said complementary sequence having the sequence of Sequence ID No:
- 102.
An oligonucleotide between 15 and 26 nucleotides in length, inclusive, said oligonucleotide having a sequence that is fully complementary to and hybridizes with Sequence ID No:
- 102.
An oligonucleotide between 15 and 26 nucleotides in length, inclusive, said oligonucleotide having a sequence that specifically hybridizes with a complementary sequence of the MDR1 gene said oligonucleotide being selected from the group consisting of Sequence ID Nos:
- 25, 26, 27, 28, 29, 30, 31, 32, 33 and 34.
Dependencies are inferred from the claim text.