Claims
- 1. A method for inhibiting the transcription or translation of mutant cytochrome c oxidase encoding genes, comprising the steps of:
a) contacting said genes with antisense sequences which are specific to said mutant sequences; and b) allowing hybridization between said target mutant cytochrome c oxidase gene and said antisense sequences under conditions under which said antisense sequences bind to and inhibit transcription or translation of said target mutant cytochrome c oxidase genes without preventing transcription or translation of wild-type cytochrome c oxidase genes.
- 2. The method of claim 1 wherein Alzheimer's disease is treated and wherein said cytochrome c oxidase genes contain mutations at one or more codons selected from the group of:
(a) codon 155, codon 167, codon 178, codon 193, codon 194, and codon 415 of the cytochrome c oxidase I gene; and (b) codon 20, codon 22, codon 68, codon 71, codon 74, codon 90, codon 95, codon 110, and codon 146 of the cytochrome c oxidase II gene.
- 3. A probe for detection of a disease state associated with one or more mutations in mitochondrial cytochrome c oxidase genes comprising a nucleotide sequence complementary to either of the sense and anti-sense strands of said one or more mutations in said mitochondrial cytochrome c oxidase genes.
- 4. The probe of claim 3 wherein said probe includes a region complementary to the sense and anti-sense strands of one or more codons selected from the group of:
(a) codon 155, codon 167, codon 178, codon 193, codon 194, and codon 415 of the cytochrome c oxidase I gene; and (b) codon 20, codon 22, codon 68, codon 71, codon 74, codon 90, codon 95, codon 110, and codon 146 of the cytochrome c oxidase II gene.
- 5. A kit comprising a probe for detection of an Alzheimer's disease genotype, said probe comprising a nucleotide sequence complementary to either of the sense and anti-sense strands of a mitochondrial cytochrome c oxidase gene.
- 6. The kit of claim 5, wherein said probe includes a region complementary to the sense and anti-sense strands of one or more codons selected from the group of:
(a) codon 155, codon 167, codon 178, codon 193, codon 194, and codon 415 of the cytochrome c oxidase I gene; and (b) codon 20, codon 22, codon 68, codon 71, codon 74, codon 90, codon 95, codon 110, and codon 146 of the cytochrome c oxidase II gene.
- 7. A therapeutic composition comprising antisense sequences which are specific to mutant cytochrome c oxidase genes or mutant messenger RNA transcribed therefrom, said antisense sequences adapted to bind to and inhibit transcription or translation of said target mutant cytochrome c oxidase genes without preventing transcription or translation of wild-type cytochrome c oxidase genes.
- 8. The therapeutic composition of claim 7, wherein Alzheimer's disease is treated and wherein said cytochrome c oxidase genes contain mutations at one or more codons selected from the group of:
(a) codon 155, codon 167, codon 178, codon 193, codon 194, and codon 415 of the cytochrome c oxidase I gene; and (b) codon 20, codon 22, codon 68, codon 71, codon 74, codon 90, codon 95, codon 110, and codon 146 of the cytochrome c oxidase II gene.
- 9. A method for detecting the presence of Alzheimer's disease in a subject, comprising the steps of:
a) obtaining a biological sample containing mitochondria from said subject; and b) interrogating at least one variant polypeptide, arising from one or more mutations in one or more subunits of mitochondrial cytochrome c oxidase genes, which correlates with the presence of Alzheimer's disease.
- 10. The method of claim 9, wherein said mutation is interrogated using monoclonal antibodies or polyclonal antibodies.
- 11. A ribozyme adapted to hybridize to and cleave mitochondrial mRNA molecules that encode for mutant cytochrome c oxidase subunits.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation of co-pending U.S. patent application Ser. No. 09/448,312, filed Nov. 23, 1999, now allowed; which is a continuation of U.S. patent application Ser. No. 08/413,740, filed Mar. 30, 1995 and issued as U.S. Pat. No. 6,171,859 on Jan. 9, 2001; which is a continuation-in-part of U.S. patent application Ser. No. 08/219,842 filed Mar. 30, 1994, and issued as U.S. Pat. No. 5,565,323 on Oct. 15, 1996; the disclosures of which are herein incorporated by reference in their entirety.
Continuations (2)
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Number |
Date |
Country |
Parent |
09448312 |
Nov 1999 |
US |
Child |
09978600 |
Oct 2001 |
US |
Parent |
08413740 |
Mar 1995 |
US |
Child |
09448312 |
Nov 1999 |
US |
Continuation in Parts (1)
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Date |
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08219842 |
Mar 1994 |
US |
Child |
08413740 |
Mar 1995 |
US |