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WO2001081361B1 - Compositions and method for diagnosing and treating conditions, disorders, or diseases involving cell death - Google Patents

Compositions and method for diagnosing and treating conditions, disorders, or diseases involving cell death

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Publication number
WO2001081361B1
WO2001081361B1 PCT/US2001/011501 US0111501W WO0181361B1 WO 2001081361 B1 WO2001081361 B1 WO 2001081361B1 US 0111501 W US0111501 W US 0111501W WO 0181361 B1 WO0181361 B1 WO 0181361B1
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WO
WIPO (PCT)
Prior art keywords
seq
acid sequence
nucleic acid
sequence
protective
Prior art date
Application number
PCT/US2001/011501
Other languages
French (fr)
Other versions
WO2001081361A8 (en
WO2001081361A1 (en
Inventor
Stuart D Portbury
Kasturi Puranam
Lawrence C Katz
Donald C Lo
Shawn Barney
Mary Beth Thomas
Original Assignee
Cogent Neuroscience Inc
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Publication date
Application filed by Cogent Neuroscience Inc filed Critical Cogent Neuroscience Inc
Priority to AU2001256998A priority Critical patent/AU2001256998A1/en
Publication of WO2001081361A1 publication Critical patent/WO2001081361A1/en
Publication of WO2001081361A8 publication Critical patent/WO2001081361A8/en
Publication of WO2001081361B1 publication Critical patent/WO2001081361B1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747Apoptosis related proteins
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals comprising random inserted nucleic acids (transgenic)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The present invention relates to compositions and methods for the treatment and diagnosis of conditions, disorders, or diseases involving cell death, including, but not limited to, neurological disorders such as stroke. The invention encompasses protective nucleic acids which, when introduced into a cell predisposed to undergo cell death or in the process of undergoing cell death, prevent, delay, or rescue the cell from death relative to a corresponding cell into which no exogenous nucleic acids have been introduced.

Claims

receve y e nerna ona ureau on e ruary . . ; original claims 1, 2, 17, 20, 33, 43, 48, 49, 51, 59 and 60 amended; remaining claims unchanged (19 page)]
1. (Amended) An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide comprising: (a) theaminoacidsequenceofSEQLDNO:3,SEQIDNO:5, SEQ ID
NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQIDNO: 13, SEQ ID NO: 15, SEQIDNO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ LD NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, or SEQ ID NO: 31 ;
(b) the amino acid sequence of SEQ LD NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ LD NO: 46, SEQ ID NO:
48, SEQ LD NO: 50, SEQ ID NO: 52, SEQ LD NO: 54, or SEQ ID NO: 56;
(c) the amino acid sequence of SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 71, SEQ LD NO: 73, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 93, SEQ
ID NO: 95, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 105, SEQ ID NO: 107, SEQ ID NO: 109, SEQIDNO: 111, SEQ ID NO: 113, SEQ ID NO: 115, SEQIDNO: 117,SEQIDNO: 119,SEQIDNO: 121, SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQIDNO: 131. SEQIDNO: 133, SEQ ID NO: 135, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ID NO: 141, SEQ ID NO: 143, SEQ ID
NO: 145, SEQ E) NO: 147, SEQIDNO: 149, SEQIDNO: 151, SEQ ID NO: 153, SEQ ID NO: 155, SEQ ID NO: 157, SEQ LD NO: 159, SEQ ID NO: 161, SEQ ID NO: 163, or SEQ ID NO: 165;
(d) the amino acid sequence of SEQ ID NO: 168, SEQ ID NO: 170, SEQ ID NO: 172, SEQ ID NO: 174, SEQ ID NO: 176, SEQ ID NO: 178, SEQ ID NO: 180, SEQ
ID NO: 182, SEQIDNO: 184, SEQIDNO: 186, SEQ ID NO: 188, SEQIDNO: 190, SEQ ID NO: 192, SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 200, SEQ ID NO: 202, SEQ ID NO: 204, SEQ ID NO: 206, SEQ LD NO: 208, SEQ ID NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, or SEQ LD NO: 216, or SEQ ID NO: 218; or (e) the amino acid sequence ofSEQLD NO: 221, SEQ ID NO: 223, SEQ
LD NO: 225, SEQ ID NO: 227, SEQ ID NO: 229, SEQ ID NO: 231, SEQ ID NO: 233, SEQ
118 ID NO: 235, SEQ ID NO: 237, SEQ LD NO: 239, SEQ ID NO: 241, SEQ ID NO: 243, SEQ ID NO: 245, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO: 251, SEQ ID NO: 253, SEQ ID NO: 255, SEQ LD NO: 257, SEQ LD NO: 259, SEQ ID NO: 261, SEQ ID NO: 263, SEQ ID NO: 265, or SEQ LD NO: 267.
2. (Amended) An isolated nucleic acid molecule comprising:
(a) the nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ LD NO: 6, SEQ ID NO: 8, SEQ LD NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ LD NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, or SEQ LD NO: 30;
(b) the nucleic acid sequence of SEQ LD NO: 33, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 39, SEQ LD NO: 41, SEQ LD NO: 43, SEQ ID NO: 45, SEQ LD NO: 47, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: SEQ ID NO: 53, or SEQ ID NO: 55;
(c) the nucleic acid sequence of SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO:
72, SEQ ID NO: 74, SEQ ID NO: 76, SEQ LD NO: 78, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 84, SEQ ID NO: 86, SEQ ID NO: 88, SEQ ID NO: 90, SEQ ID NO: 92, SEQ ID NO: 94, SEQ ID NO: 96, SEQ ED NO: 98, SEQ ID NO: 100, SEQ ID NO: 102, SEQ ID NO: 104, SEQ ID NO: 106, SEQ ID NO: 108 SEQ ID NO: 1 10, SEQ ID NO: 112, SEQ ID NO: 114, SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 120, SEQ ID NO: 122, SEQ ED
NO: 124, SEQ ID NO: 146, SEQ ED NO: 148, SEQ ID NO: 130, SEQ ID NO: 132, SEQ ED NO: 134, SEQ ED NO: 136, SEQ ED NO: 138, SEQ ED NO: 140, SEQ D NO: 142, SEQ ED NO: 144, SEQ ED NO: 146, SEQ ED NO: 148, SEQ ED NO: 150, SEQ ED NO: 152, SEQ ED NO: 154, SEQ ED NO: 156, SEQ ED NO: 158, SEQ ED NO: 160, SEQ ED NO: 162, or SEQ ED NO: 164;
(d) the nucleic acid sequence of SEQ ED NO: 167, SEQ ED NO: 169, SEQ ED NO: 171, SEQ ED NO: 173, SEQ ED NO: 175, SEQ ED NO: 177, SEQ ED NO: 179, SEQ ED NO: 181, SEQ ED NO: 183, SEQ ED NO: 185, SEQ ED NO: 187, SEQ ED NO: 189, SEQ ED NO: 191, SEQ ED NO: 193, SEQ ED NO: 195, SEQ ED NO: 197, SEQ ED NO: 199, SEQ ED NO: 201, SEQ ED NO: 203, SEQ ED NO: 205, SEQ ED NO: 207, SEQ ED NO: 209, SEQ
ED NO: 211, SEQ ED NO: 213, SEQ ED NO: 215, or SEQ ED NO: 217;
119 (e) the nucleic acid sequence of SEQ ID NO: 220, SEQ ED NO: 222, SEQ ID NO: 224, SEQ ED NO: 226, SEQ ID NO: 228, SEQ ED NO: 230, SEQ ED NO: 232, SEQ ED NO: 234, SEQ ED NO: 236, SEQ ED NO: 238, SEQ ED NO: 240, SEQ ID NO: 242, SEQ ID NO: 244, SEQ ID NO: 246, SEQ ID NO: 248, SEQ ED NO: 250, SEQ ED NO: 252, SEQ ID NO: 254, SEQ ID NO: 256, SEQ ID NO: 258, SEQ ID NO: 260, SEQ ID NO: 262, SEQ
ID NO: 264, or SEQ ID NO: 266; or
(f) the nucleic acid sequence of SEQ ID NO: 1 , SEQ ID NO: 32, SEQ ID NO: 57, SEQ ID NO: 166, or SEQ ID NO: 219.
3. An isolated nucleic acid molecule comprising a complement of the nucleic acid molecule of any one of Claims 1 and 2.
4. An isolated nucleic acid molecule which hybridizes to the nucleic acid molecule of Claim 3 under highly stringent conditions.
5. An isolated nucleic acid molecule which hybridizes to the nucleic acid molecule of Claim 3 under moderately stringent conditions.
6. The isolated nucleic acid molecule of Claim 4, wherein said isolated nucleic acid molecule encodes a protective sequence product.
7. The isolated nucleic acid molecule of Claim 5, wherein said isolated nucleic acid molecule encodes a protective sequence product.
8. A vector comprising the nucleic acid of any one of Claims 1 and 2.
9. The vector of claim 8, wherein said vector is a viral vector.
10. An expression vector comprising the nucleic acid of any one of Claims 1 and 2 operatively associated with a regulatory nucleic acid controlling the expression of the nucleic acid in a host cell.
120
11. A host cell genetically engineered to contain the nucleic acid of any one of Claims 1 and 2.
12. A host cell genetically engineered to express the nucleic acid of any one of Claims 1 and 2 operatively associated with a regulatory nucleic acid controlling expression of the nucleic acid in said host cell.
13. The host cell of Claim 12, wherein said host cell is a neuronal cell.
14. The host cell of Claim 13, wherein said neuronal cell is a PC- 12 cell or a primary dissociated neuron.
15. A transgenic, non-human animal which has been genetically engineered to contain a transgene comprising the nucleic acid of any one of Claims 1 and 2.
16. The transgenic, non-human animal of Claim 15, wherein the transgene is expressed.
17. An isolated polypeptide comprising: (a) the amino acid sequence of SEQ ED NO: 3, SEQ ID NO: 5, SEQ ID
NO: 7, SEQ ED NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ED NO: 29, or SEQ ED NO: 31;
(b) the amino acid sequence of SEQ ID NO: 34, SEQ ID NO: 36, SEQ ED NO: 38, SEQ ED NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO:
48, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, or SEQ JD NO: 56;
(c) the amino acid sequence of SEQ ID NO: 59, SEQ JD NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ JD NO: 67, SEQ ED NO: 69, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ED NO: 75, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO: 81, SEQ JD NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ JD NO: 89, SEQ ED NO: 91, SEQ JD NO: 93, SEQ
ID NO: 95, SEQ ID NO: 97, SEQ JD NO: 99, SEQ ED NO: 101, SEQ ID NO: 103, SEQ ID
121 O: 105, SEQ JD NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID O: 115, SEQ ID NO: 117, SEQ ED NO: 119, SEQ ED NO: 121, SEQ 3D NO: 123, SEQ ED NO: 125, SEQ ED NO: 127, SEQ ID NO: 129, SEQ JD NO: 131, SEQ JD NO: 133, SEQ ED NO: 135, SEQ ED NO: 137, SEQ ED NO: 139, SEQ ED NO: 141, SEQ ED NO: 143, SEQ ED NO: 145, SEQ ID NO: 147, SEQ ED NO: 149, SEQ ED NO: 151, SEQ ED NO: 153, SEQ ED NO: 155, SEQ ED NO: 157, SEQ ED NO: 159, SEQ ED NO: 161, SEQ ED NO: 163, or SEQ ED NO: 165;
(d) the amino acid sequence of SEQ ED NO: 168, SEQ ED NO: 170, SEQ ID NO: 172, SEQ ID NO: 174, SEQ ED NO: 176, SEQ ED NO: 178, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 184, SEQ ED NO: 186, SEQ ED NO: 188, SEQ ED NO: 190, SEQ JD NO: 192, SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 200, SEQ ID NO: 202, SEQ ED NO: 204, SEQ JD NO: 206, SEQ ED NO: 208, SEQ ED NO: 210, SEQ ID NO: 212, SEQ ID NO: 214, or SEQ ID NO: 216, or SEQ ID NO: 218; or
(e) the amino acid sequence of SEQ ID NO: 221, SEQ ID NO: 223, SEQ ID NO: 225, SEQ ID NO: 227, SEQ JD NO: 229, SEQ JD NO: 231, SEQ JD NO: 233, SEQ JD NO: 235, SEQ JD NO: 237, SEQ ED NO: 239, SEQ JD NO: 241, SEQ ID NO: 243, SEQ ED NO: 245, SEQ ID NO: 247, SEQ ED NO: 249, SEQ ED NO: 251, SEQ ID NO: 253, SEQ ID NO: 255, SEQ ID NO: 257, SEQ JD NO: 259, SEQ ED NO: 261, SEQ ID NO: 263, SEQ HD NO: 265, or SEQ ED NO: 267.
18. An isolated polypeptide comprising an amino acid sequence encoded by the isolated nucleic acid molecule of Claim 4.
19. An isolated polypeptide comprising an amino acid sequence encoded by the isolated nucleic acid molecule of Claim 5.
20. An isolated fusion polypeptide comprising a fusion peptide and an amino acid sequence comprising:
(a) the amino acid sequence of SEQ ID NO: 3, SEQ JD NO: 5, SEQ ID NO: 7, SEQ JD NO: 9, SEQ JD NO: 11, SEQ ED NO: 13, SEQ ID NO: 15, SEQ ID NO: 17,
122 SEQ ID NO: 19, SEQ ED NO: 21, SEQ ED NO: 23, SEQ ED NO: 25, SEQ ED NO: 27, SEQ LD NO: 29, or SEQ ED NO: 31 ;
(b) the amino acid sequence of SEQ ED NO: 34, SEQ ED NO: 36, SEQ ED NO: 38, SEQ ED NO: 40, SEQ ED NO: 42, SEQ D NO: 44, SEQ ED NO: 46, SEQ ED NO: 48, SEQ ED NO: 50, SEQ ED NO: 52, SEQ ED NO: 54, or SEQ ED NO: 56;
(c) the amino acid sequence of SEQ ED NO: 59, SEQ ED NO: 61, SEQ ED NO: 63, SEQ ED NO: 65, SEQ ED NO: 67, SEQ ED NO: 69, SEQ ED NO: 71, SEQ ED NO: 73, SEQ ED NO: 75, SEQ ID NO: 77, SEQ ED NO: 79, SEQ ED NO: 81, SEQ ED NO: 83, SEQ ED NO: 85, SEQ ED NO: 87, SEQ ED NO: 89, SEQ ED NO: 91, SEQ ED NO: 93, SEQ ED NO: 95, SEQ ED NO: 97, SEQ ED NO: 99, SEQ ED NO: 101, SEQ ED NO: 103, SEQ ED
NO: 105, SEQ ED NO 107, SEQ ED NO: 109, SEQ ED NO: 1 1 1, SEQ ED NO: 113, SEQ ED NO: 115, SEQ ED NO 117, SEQ ID NO: 1 19, SEQ ED NO: 121, SEQ ED NO: 123, SEQ ED NO: 125, SEQ ED NO 127, SEQ HD NO: 129, SEQ ED NO: 131, SEQ ID NO: 133, SEQ ED NO: 135, SEQ ED NO 137, SEQ ED NO: 139, SEQ ED NO: 141, SEQ ED NO: 143, SEQ ED NO: 145, SEQ JD NO 147, SEQ ED NO: 149. SEQ JD NO: 151, SEQ JD NO: 153, SEQ ED NO: 155, SEQ JD NO 157, SEQ ED NO: 159, SEQ JD NO: 161 , SEQ ED NO: 163, or SEQ
ED NO: 165;
(d) the amino acid sequence of SEQ ED NO: 168, SEQ ED NO: 170, SEQ ED NO: 172, SEQ ID NO: 174, SEQ ED NO: 176, SEQ ED NO: 178, SEQ ED NO: 180, SEQ ED NO: 182, SEQ ED NO: 184, SEQ ED NO: 186, SEQ ED NO: 188, SEQ ID NO: 190, SEQ HD NO: 192, SEQ ID NO: 194, SEQ ED NO: 196, SEQ ED NO: 198, SEQ ED NO: 200, SEQ ED NO: 202, SEQ ED NO: 204, SEQ ED NO: 206, SEQ ED NO: 208, SEQ ED NO: 210, SEQ ED NO: 212, SEQ ED NO: 214, or SEQ ED NO: 216, or SEQ ED NO: 218; or
(e) the amino acid sequence of SEQ ED NO: 221, SEQ ED NO: 223, SEQ ED NO: 225, SEQ ED NO: 227, SEQ ID NO: 229, SEQ ID NO: 231, SEQ HD NO: 233, SEQ ED NO: 235, SEQ ED NO: 237, SEQ ED NO: 239, SEQ ED NO: 241, SEQ ED NO: 243, SEQ ED NO: 245, SEQ JD NO: 247, SEQ JD NO: 249, SEQ ED NO: 251, SEQ JD NO: 253, SEQ ED NO: 255, SEQ ED NO: 257, SEQ ED NO: 259, SEQ JD NO: 261, SEQ ED NO: 263, SEQ ED NO: 265, or SEQ ED NO: 267.
123
21. An isolated fusion polypeptide comprising a fusion peptide and an amino acid sequence encoded by the isolated nucleic acid molecule of Claim 4.
22. An isolated fusion polypeptide comprising a fusion peptide and an amino acid sequence encoded by the isolated nucleic acid molecules of Claim 5.
23. An antibody which binds to the isolated polypeptide of Claim 17.
24. A method for diagnosing a protective sequence-mediated condition, disorder or disease in an individual comprising obtaining a biological sample from said individual; contacting said biological sample with the antibody according to claim 23; wherein if said antibody interacts with said biological sample, but does not interact with a biological sample from a control individual not undergoing a protective sequence-mediated condition, disorder or disease, then a protective sequence-mediated condition, disorder or disease has been diagnosed.
25. A diagnostic kit for detecting a protective sequence-mediated condition, disorder or disease in an individual comprising a reagent in suitable packaging, wherein said reagent comprises the antibody according to claim 23.
26. A method for treating, ameliorating or preventing a protective sequence- mediated condition, disorder or disease in an individual comprising administering to the individual a compound which modulates the function, activity, expression and/or level of a protective sequence in a cell, cells, tissue, organ, organism or individual.
27. The method of Claim 26, wherein the compound inhibits the function, activity, expression and/or level of a protective sequence in a cell, cells, tissue, organ, organism or individual.
124
28. The method of Claim 26, wherein the compound enhances or potentiates the function, activity, expression and/or level of a protective sequence in a cell, cells, tissue, organ, organism or individual.
29. The methods of any one of Claims 26-28, wherein the compound is selected from the group consisting of a small organic molecule, an antibody, a ribozyme, an antisense molecule, and combinations thereof.
30. The method of any one of Claims 26-28, wherein the protective sequence- mediated condition, disorder, or disease is a condition, disorder, or disease of the central nervous system.
31. The method of Claim 30, wherein the central nervous system condition is an ischemia-related condition.
32. The method of Claim 31 , wherein the central nervous system condition is a stroke.
33. The method of Claim 26, wherein the protective sequence encodes a polypeptide comprising:
(a) the amino acid sequence of SEQ ID NO: 3, SEQ ED NO: 5, SEQ ED NO: 7, SEQ HD NO: 9, SEQ ED NO: 11, SEQ ED NO: 13, SEQ JD NO: 15, SEQ ID NO: 17, SEQ DD NO: 19, SEQ HD NO: 21, SEQ ID NO: 23, SEQ ED NO: 25, SEQ ED NO: 27, SEQ ED NO: 29, or SEQ ED NO: 31 ; (b) the amino acid sequence of SEQ ED NO: 34, SEQ ED NO: 36, SEQ ED
NO: 38, SEQ ED NO: 40, SEQ HD NO: 42, SEQ JD NO: 44, SEQ ID NO: 46, SEQ JD NO: 48, SEQ H NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, or SEQ ED NO: 56;
(c) the amino acid sequence of SEQ ED NO: 59, SEQ ED NO: 61, SEQ ED NO: 63, SEQ ID NO: 65, SEQ ED NO: 67, SEQ JD NO: 69, SEQ ED NO: 71, SEQ ED NO: 73, SEQ ID NO: 75, SEQ ED NO: 77, SEQ ED NO: 79, SEQ ED NO: 81, SEQ ED NO: 83,
SEQ ED NO: 85, SEQ ED NO: 87, SEQ ED NO: 89, SEQ ID NO: 91, SEQ ED NO: 93, SEQ
125 ID NO: 95, SEQ JD NO: 97, SEQ JD NO: 99, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ED
NO: 105, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ED NO: 111, SEQ ED NO 113, SEQ ED NO: 115, SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 121, SEQ ID NO 123, SEQ ED
NO: 125, SEQ ED NO: 127, SEQ ID NO: 129, SEQ HD NO: 131, SEQ JD NO 133, SEQ ED NO: 135, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ED NO: 141, SEQ ED NO 143, SEQ ED
NO: 145, SEQ ED NO: 147, SEQ ED NO: 149, SEQ ED NO: 151, SEQ ED NO 153, SEQ ED NO: 155, SEQ ED NO: 157, SEQ ED NO: 159, SEQ ED NO: 161, SEQ ED NO 163, or SEQ ED NO: 165;
(d) the amino acid sequence of SEQ ID NO: 168, SEQ HD NO: 170, SEQ ED NO: 172, SEQ ED NO: 174, SEQ ED NO: 176, SEQ ED NO: 178, SEQ JD NO: 180, SEQ
ED NO: 182, SEQ ID NO: 184, SEQ HD NO: 186, SEQ ID NO: 188, SEQ HD NO: 190, SEQ ED NO: 192, SEQ HD NO: 194, SEQ HD NO: 196, SEQ HD NO: 198, SEQ ID NO: 200, SEQ ID NO: 202, SEQ JD NO: 204, SEQ ED NO: 206, SEQ ED NO: 208, SEQ ED NO: 210, SEQ ED NO: 212, SEQ ED NO: 214, or SEQ ED NO: 216, or SEQ ED NO: 218; or (e) the amino acid sequence of SEQ ED NO: 221, SEQ ID NO: 223, SEQ
ED NO: 225, SEQ ID NO: 227, SEQ ED NO: 229, SEQ ED NO: 231 , SEQ ED NO: 233, SEQ ED NO: 235, SEQ ED NO: 237, SEQ ED NO: 239, SEQ ED NO: 241 , SEQ ED NO: 243, SEQ ED NO: 245, SEQ JD NO: 247, SEQ JD NO: 249, SEQ JD NO: 251, SEQ ED NO: 253, SEQ HD NO: 255, SEQ JD NO: 257, SEQ ED NO: 259, SEQ ED NO: 261, SEQ ED NO: 263, SEQ ED NO: 265, or SEQ ED NO: 267.
34. The method of Claim 26, wherein the individual is a mammal.
35. The method of Claim 34, wherein the mammal is a human.
36. A method for treating, ameliorating, or preventing a protective sequence- mediated condition, disorder or disease in an individual comprising administering to the individual a compound which modulates the expression or activity of a protective sequence product and/or protective sequence regulatory product in the individual.
126
37. The method of Claim 36, wherein the compound inhibits the expression or activity of a protective sequence product and/or protective sequence regulatory product in the individual.
38. The method of Claim 36, wherein the compound enhances or potentiates the expression or activity of a protective sequence product and/or protective sequence regulatory product in the individual.
39. The method of Claim 36, wherein the compound is selected from the group consisting of a small organic molecule, an antibody, a ribozyme, an antisense molecule, and combinations thereof.
40. The method of Claim 36, wherein the protective sequence-mediated condition, disorder, or disease is a condition, disorder, or disease of the central nervous system.
41. The method of Claim 40, wherein the central nervous system condition is an ischemia-related condition.
42. The method of Claim 41, wherein the central nervous system condition is a stroke.
43. The method of Claim 36, wherein the protective sequence product comprises:
(a) the amino acid sequence of SEQ ID NO: 3, SEQ HD NO: 5, SEQ ED NO: 7, SEQ ED NO: 9, SEQ JD NO: 11, SEQ ED NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ED NO: 21, SEQ ED NO: 23, SEQ ED NO: 25, SEQ ED NO: 27, SEQ
ED NO: 29, or SEQ ID NO: 31 ;
(b) the amino acid sequence of SEQ ED NO: 34, SEQ ID NO: 36, SEQ ED NO: 38, SEQ ED NO: 40, SEQ ED NO: 42, SEQ ED NO: 44, SEQ ED NO: 46, SEQ ED NO: 48, SEQ ED NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, or SEQ ED NO: 56; (c) the amino acid sequence of SEQ ID NO: 59, SEQ JD NO: 61, SEQ ED
NO: 63, SEQ HD NO: 65, SEQ ID NO: 67, SEQ ED NO: 69, SEQ ID NO: 71, SEQ ED NO:
127 73, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ED NO: 79, SEQ ED NO: 81, SEQ ED NO: 83, SEQ ED NO: 85, SEQ ED NO: 87, SEQ ED NO: 89, SEQ ED NO: 91, SEQ ED NO: 93, SEQ ED NO: 95, SEQ ED NO: 97, SEQ ED NO: 99, SEQ ID NO: 101, SEQ JD NO: 103, SEQ ED NO: 105, SEQ ED NO: 107, SEQ ED NO: 109, SEQ ID NO: 111, SEQ ED NO: 113, SEQ ED NO: 115, SEQ ID NO: 117, SEQ ED NO: 119, SEQ ID NO: 121, SEQ HD NO: 123, SEQ ID
NO: 125, SEQ JD NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ED NO: 133, SEQ ED NO: 135, SEQ ED NO: 137, SEQ ED NO: 139, SEQ ED NO: 141, SEQ ID NO: 143, SEQ ED NO: 145, SEQ ED NO: 147, SEQ ED NO: 149, SEQ ED NO: 151, SEQ ED NO: 153, SEQ ED NO: 155, SEQ JD NO: 157, SEQ JD NO: 159, SEQ JD NO: 161, SEQ ED NO: 163, or SEQ ED NO: 165;
(d) the amino acid sequence of SEQ ID NO: 168, SEQ JD NO: 170, SEQ H NO: 172, SEQ ID NO: 174, SEQ JD NO: 176, SEQ HD NO: 178, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 184, SEQ ID NO: 186, SEQ ID NO: 188, SEQ HD NO: 190, SEQ ED NO: 192, SEQ ID NO: 194, SEQ ID NO: 196, SEQ JD NO: 198, SEQ ED NO: 200, SEQ ED NO: 202, SEQ ED NO: 204, SEQ ED NO: 206, SEQ ED NO: 208, SEQ JD NO: 210, SEQ
ED NO: 212, SEQ ED NO: 214, or SEQ ED NO: 216, or SEQ ED NO: 218; or
(e) the amino acid sequence of SEQ ED NO: 221, SEQ ED NO: 223, SEQ ED NO: 225, SEQ ED NO: 227, SEQ ED NO: 229, SEQ ED NO: 231 , SEQ ED NO: 233, SEQ ED NO: 235, SEQ ED NO: 237, SEQ ED NO: 239, SEQ ED NO: 241, SEQ ED NO: 243, SEQ ED NO: 245, SEQ ED NO: 247, SEQ ED NO: 249, SEQ ED NO: 251, SEQ ED NO: 253, SEQ
ED NO: 255, SEQ ED NO: 257, SEQ ID NO: 259, SEQ JD NO: 261, SEQ ED NO: 263, SEQ ID NO: 265, or SEQ ED NO: 267.
44. The method of Claim 36, wherein the individual is a mammal.
45. The method of Claim 44, wherein the mammal is a human.
46. A method for identifying a compound which modulates expression of a protective sequence comprising: (a) contacting a test compound to a cell that expresses a protective sequence;
(b) measuring a level of protective sequence expression in the cell; (c) comparing the level of protective sequence expression in the cell in the presence of the test compound to a level of protective sequence expression in the cell in the absence of the test compound, wherein if the level of protective sequence expression in the cell in the presence of the test compound differs from the level of expression of the protective sequence in the cell in the absence of the test compound, a compound that modulates expression of a protective sequence is identified.
47. The method of Claim 46, wherein the protective sequence is endogenously expressed within the cell.
48. The method of Claim 46, wherein the protective sequence encodes a polypeptide comprising:
(a) the amino acid sequence of SEQ ED NO: 3, SEQ JD NO: 5, SEQ HD NO: 7, SEQ JD NO: 9, SEQ HD NO: 11, SEQ ED NO: 13, SEQ ED NO: 15, SEQ ED NO: 17,
SEQ ED NO: 19, SEQ ED NO: 21, SEQ ED NO: 23, SEQ ED NO: 25, SEQ ED NO: 27, SEQ ED NO: 29, or SEQ ED NO: 31;
(b) the amino acid sequence of SEQ ED NO: 34, SEQ JD NO: 36, SEQ ID NO: 38, SEQ JD NO: 40, SEQ ID NO: 42, SEQ JD NO: 44, SEQ JD NO: 46, SEQ ID NO: 48, SEQ ID NO: 50, SEQ JD NO: 52, SEQ JD NO: 54, or SEQ ED NO: 56;
(c) the amino acid sequence of SEQ ED NO: 59, SEQ ED NO: 61, SEQ ED NO: 63, SEQ ED NO: 65, SEQ ED NO: 67, SEQ ED NO: 69, SEQ ED NO: 71, SEQ ED NO: 73, SEQ ED NO: 75, SEQ ED NO: 77, SEQ ED NO: 79, SEQ ED NO: 81, SEQ ED NO: 83, SEQ ED NO: 85, SEQ ED NO: 87, SEQ ED NO: 89, SEQ ED NO: 91, SEQ ED NO: 93, SEQ ID NO: 95, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ED
NO: 105, SEQ ED NO: 107, SEQ HD NO: 109, SEQ JD NO: 111, SEQ ID NO: 113, SEQ ED NO: 115, SEQ ED NO: 117, SEQ ED NO: 119, SEQ ID NO: 121, SEQ ED NO: 123, SEQ ID NO: 125, SEQ JD NO: 127, SEQ ED NO: 129, SEQ ED NO: 131, SEQ ED NO: 133, SEQ HD NO: 135, SEQ ED NO: 137, SEQ JD NO: 139, SEQ ID NO: 141, SEQ ED NO: 143, SEQ ED NO: 145, SEQ JD NO: 147, SEQ ID NO: 149, SEQ ED NO: 151, SEQ ED NO: 153, SEQ ED
NO: 155, SEQ ED NO: 157, SEQ ED NO: 159, SEQ ED NO: 161, SEQ ED NO: 163, or SEQ ED NO: 165;
129 (d) the amino acid sequence of SEQ ED NO: 168, SEQ JD NO: 170, SEQ ED NO: 172, SEQ ED NO: 174, SEQ ED NO: 176, SEQ ED NO: 178, SEQ ED NO: 180, SEQ E NO: 182, SEQ ID NO: 184, SEQ ED NO: 186, SEQ ID NO: 188, SEQ HD NO: 190, SEQ ED NO: 192, SEQ ED NO: 194, SEQ ED NO: 196, SEQ ED NO: 198, SEQ ED NO: 200, SEQ HD NO: 202, SEQ ED NO: 204, SEQ ED NO: 206, SEQ ED NO: 208, SEQ ED NO: 210, SEQ ED NO: 212, SEQ ED NO: 214, or SEQ ED NO: 216, or SEQ ED NO: 218; or
(e) the amino acid sequence of SEQ ED NO: 221, SEQ ED NO: 223, SEQ ED NO: 225, SEQ ED NO: 227, SEQ ID NO: 229, SEQ JD NO: 231 , SEQ JD NO: 233, SEQ ED NO: 235, SEQ ED NO: 237, SEQ ED NO: 239, SEQ ED NO: 241, SEQ ED NO: 243, SEQ ED NO: 245, SEQ ED NO: 247, SEQ ED NO: 249, SEQ ED NO: 251, SEQ ED NO: 253, SEQ ID NO: 255, SEQ JD NO: 257, SEQ HD NO: 259, SEQ ID NO: 261, SEQ ED NO: 263, SEQ ED NO: 265, or SEQ ED NO: 267.
49. The method of Claim 46, wherein the protective sequence comprises:
(a) the nucleic acid sequence of SEQ ID NO: 2, SEQ JD NO: 4, SEQ JD NO: 6, SEQ ED NO: 8, SEQ ED NO: 10, SEQ ED NO: 12, SEQ ED NO: 14, SEQ ED NO: 16, SEQ ED NO: 18, SEQ ED NO: 20, SEQ JD NO: 22, SEQ ED NO: 24, SEQ ED NO: 26, SEQ ED NO: 28, or SEQ ED NO: 30;
(b) the nucleic acid sequence of SEQ ED NO: 33, SEQ ED NO: 35, SEQ ED NO: 37, SEQ ED NO: 39, SEQ ED NO: 41, SEQ ED NO: 43, SEQ ED NO: 45, SEQ ED NO: 47, SEQ HD NO: 49, SEQ JD NO: 51, SEQ ED NO: SEQ ED NO: 53, or SEQ JD NO: 55;
(c) the nucleic acid sequence of SEQ ED NO: 58, SEQ JD NO: 60, SEQ ED NO: 62, SEQ ED NO: 64, SEQ ED NO: 66, SEQ ED NO: 68, SEQ ID NO: 70, SEQ ED NO: 72, SEQ ED NO: 74, SEQ ED NO: 76, SEQ ED NO: 78, SEQ ED NO: 80, SEQ ED NO: 82, SEQ ED NO: 84, SEQ ED NO: 86, SEQ ED NO: 88, SEQ ED NO: 90, SEQ JD NO: 92, SEQ HD NO: 94, SEQ ID NO: 96, SEQ JD NO: 98, SEQ ED NO: 100, SEQ JD NO: 102, SEQ ED
NO: 104, SEQ ED NO: 106, SEQ ED NO 108 SEQ ED NO: 1 10, SEQ ED NO: 112, SEQ ED NO: 114, SEQ JD NO: 116, SEQ JD NO 118, SEQ ED NO: 120, SEQ HD NO: 122, SEQ ED NO: 124, SEQ ID NO: 146, SEQ ED NO 148, SEQ ED NO: 130, SEQ ED NO: 132, SEQ ED NO: 134, SEQ ED NO: 136, SEQ ED NO 138, SEQ ED NO: 140, SEQ ED NO: 142, SEQ ED NO: 144, SEQ ED NO: 146, SEQ ID NO 148, SEQ ED NO: 150, SEQ ED NO: 152, SEQ ED
130 NO: 154, SEQ ID NO: 156, SEQ JD NO: 158, SEQ ID NO: 160, SEQ JD NO: 162, or SEQ ED NO: 164;
(d) the nucleic acid sequence of SEQ ED NO: 167, SEQ ED NO: 169, SEQ ED NO: 171, SEQ ED NO: 173, SEQ ED NO: 175, SEQ ED NO: 177, SEQ ED NO: 179, SEQ ID NO: 181, SEQ ID NO: 183, SEQ ID NO: 185, SEQ HD NO: 187, SEQ HD NO: 189, SEQ
H NO: 191, SEQ ED NO: 193, SEQ ED NO: 195, SEQ ED NO: 197, SEQ ED NO: 199, SEQ ED NO: 201, SEQ ED NO: 203, SEQ ED NO: 205, SEQ ED NO: 207, SEQ ED NO: 209, SEQ ED NO: 211, SEQ ED NO: 213, SEQ ED NO: 215, or SEQ ED NO: 217;
(e) the nucleic acid sequence of SEQ ED NO: 220, SEQ ED NO: 222, SEQ ED NO: 224, SEQ ED NO: 226, SEQ JD NO: 228, SEQ JD NO: 230, SEQ ID NO: 232, SEQ
ID NO: 234, SEQ JD NO: 236, SEQ ID NO: 238, SEQ ID NO: 240, SEQ ID NO: 242, SEQ HD NO: 244, SEQ ID NO: 246, SEQ ED NO: 248, SEQ ED NO: 250, SEQ ED NO: 252, SEQ HD NO: 254, SEQ JD NO: 256, SEQ JD NO: 258, SEQ ED NO: 260, SEQ ED NO: 262, SEQ ED NO: 264, or SEQ ED NO: 266; or (f) the nucleic acid sequence of SEQ ED NO: 1 , SEQ ED NO: 32, SEQ ED
NO: 57, SEQ JD NO: 166, or SEQ JD NO: 219.
50. A method for identifying a compound which modulates expression, function or activity of a protective sequence product or protective sequence regulatory element comprising:
(a) contacting a test compound to a cell that expresses a protective sequence product or protective sequence regulatory element;
(b) measuring a level of protective sequence product or protective sequence regulatory element expression, function or activity in the cell; (c) comparing the level of protective sequence product or protective sequence regulatory element expression, function or activity in the cell in the presence of the test compound to a level of protective sequence product or protective sequence regulatory element expression or activity in the cell in the absence of the test compound, wherein if the level of protective sequence product or protective sequence regulatory element expression, function or activity in the cell in the presence of the test compound differs from the level of protective sequence product or protective sequence regulatory
131 element expression, function or activity in the cell in the absence of the test compound, a compound that modulates expression or activity of a protective sequence product or protective sequence regulatory element is identified.
51. The method of Claim 50, wherein the protective sequence product or protective sequence regulatory element comprises:
(a) the nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ HD NO: 6, SEQ ED NO: 8, SEQ ID NO: 10, SEQ ED NO: 12, SEQ ED NO: 14, SEQ ED NO: 16, SEQ ED NO: 18, SEQ JD NO: 20, SEQ JD NO: 22, SEQ ED NO: 24, SEQ ED NO: 26, SEQ ED NO: 28, or SEQ ID NO: 30;
(b) the nucleic acid sequence of SEQ ID NO: 33, SEQ ID NO: 35, SEQ JD NO: 37, SEQ ED NO: 39, SEQ ED NO: 41, SEQ ED NO: 43, SEQ JD NO: 45, SEQ JD NO: 47, SEQ ED NO: 49, SEQ ED NO: 51, SEQ ED NO: SEQ ED NO: 53, or SEQ ED NO: 55;
(c) the nucleic acid sequence of SEQ ED NO: 58, SEQ ED NO: 60, SEQ ED NO: 62, SEQ ED NO: 64, SEQ ED NO: 66, SEQ HD NO: 68, SEQ JD NO: 70, SEQ JD NO:
72, SEQ ED NO: 74, SEQ ED NO: 76, SEQ ED NO: 78, SEQ ED NO: 80, SEQ JD NO: 82, SEQ ED NO: 84, SEQ ED NO: 86, SEQ ED NO: 88, SEQ ED NO: 90, SEQ JD NO: 92, SEQ HD NO: 94, SEQ HD NO: 96, SEQ JD NO: 98, SEQ ED NO: 100, SEQ ED NO: 102, SEQ ED NO: 104, SEQ ED NO: 106, SEQ ED NO: 108 SEQ ID NO: 110, SEQ JD NO: 112, SEQ ED NO: 114, SEQ ED NO: 116, SEQ ED NO: 118, SEQ ED NO: 120, SEQ ED NO: 122, SEQ ED
NO: 124, SEQ ED NO: 146, SEQ ED NO: 148, SEQ ED NO: 130, SEQ JD NO: 132, SEQ JD NO: 134, SEQ JD NO: 136, SEQ ED NO: 138, SEQ ID NO: 140, SEQ JD NO: 142, SEQ JD NO: 144, SEQ ID NO: 146, SEQ JD NO: 148, SEQ ID NO: 150, SEQ JD NO: 152, SEQ JD NO: 154, SEQ ED NO: 156, SEQ ED NO: 158, SEQ ED NO: 160, SEQ ED NO: 162, or SEQ ED NO: 164;
(d) the nucleic acid sequence of SEQ ED NO: 167, SEQ ED NO: 169, SEQ ED NO: 171, SEQ JD NO: 173, SEQ JD NO: 175, SEQ ED NO: 177, SEQ ED NO: 179, SEQ ID NO: 181, SEQ JD NO: 183, SEQ ED NO: 185, SEQ ED NO: 187, SEQ JD NO: 189, SEQ HD NO: 191, SEQ ED NO: 193, SEQ ED NO: 195, SEQ ED NO: 197, SEQ JD NO: 199, SEQ ED NO: 201, SEQ ED NO: 203, SEQ JD NO: 205, SEQ JD NO: 207, SEQ ED NO: 209, SEQ
HD NO: 211, SEQ ED NO: 213, SEQ ED NO: 215, or SEQ ED NO: 217; or
132 (e) the nucleic acid sequence of SEQ ED NO: 220, SEQ ED NO: 222, SEQ ED NO: 224, SEQ ED NO: 226, SEQ JD NO: 228, SEQ ID NO: 230, SEQ ID NO: 232, SEQ ID NO: 234, SEQ ED NO: 236, SEQ ED NO: 238, SEQ ED NO: 240, SEQ ID NO: 242, SEQ ID NO: 244, SEQ ID NO: 246, SEQ HD NO: 248, SEQ ID NO: 250, SEQ ID NO: 252, SEQ ID NO: 254, SEQ JD NO: 256, SEQ ID NO: 258, SEQ ED NO: 260, SEQ ED NO: 262, SEQ
ED NO: 264, or SEQ ED NO: 266.
52. A method for transferring a protective sequence into a cell comprising contacting the cell with a nucleic acid comprising a protective sequence such that the protective sequence is transferred into the cell.
53. The method of Claim 52 wherein the protective sequence is expressed in the cell.
54. The method of Claim 52 wherein the protective sequence delays and/or prevents the cell from undergoing cell death.
55. A method for modulating the function, activity, expression and/or level of a protective sequence in a cell comprising administering to the cell a compound which modulates the function, activity, expression and/or level of a protective sequence in the cell.
56. The method of Claim 55, wherein the compound inhibits the function, activity, expression and/or level of a protective sequence in the cell.
57. The method of Claim 55, wherein the compound enhances or potentiates the function, activity, expression and/or level of a protective sequence in the cell.
58. The methods of any one of Claims 55-57, wherein the compound is selected from the group consisting of a small organic molecule, an antibody, a ribozyme, an antisense molecule, and combinations thereof.
133
59. The method of Claim 55, wherein the protective sequence encodes a polypeptide comprising:
(a) the amino acid sequence of SEQ ED NO: 3, SEQ ED NO: 5, SEQ ED NO: 7, SEQ ED NO: 9, SEQ ED NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ H NO: 19, SEQ ED NO: 21, SEQ ED NO: 23, SEQ ED NO: 25, SEQ JD NO: 27, SEQ
H NO: 29, or SEQ ID NO: 31 ;
(b) the amino acid sequence of SEQ ED NO: 34, SEQ JD NO: 36, SEQ ED NO: 38, SEQ JD NO: 40, SEQ JD NO: 42, SEQ ED NO: 44, SEQ ED NO: 46, SEQ ED NO: 48, SEQ HD NO: 50, SEQ ED NO: 52, SEQ ED NO: 54, or SEQ ED NO: 56; (c) the amino acid sequence of SEQ ED NO: 59, SEQ HD NO: 61, SEQ ED
NO: 63, SEQ ED NO: 65, SEQ JD NO: 67, SEQ JD NO: 69, SEQ ED NO: 71, SEQ ED NO: 73, SEQ ED NO: 75, SEQ ED NO: 77, SEQ ED NO: 79, SEQ ED NO: 81, SEQ ED NO: 83, SEQ ED NO: 85, SEQ ED NO: 87, SEQ ID NO: 89, SEQ HD NO: 91, SEQ ID NO: 93, SEQ HD NO: 95, SEQ JD NO: 97, SEQ JD NO: 99, SEQ ED NO: 101, SEQ ED NO: 103, SEQ ED NO: 105, SEQ JD NO: 107, SEQ HD NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID
NO: 115, SEQ JD NO: 117, SEQ HD NO: 119, SEQ ED NO: 121, SEQ ED NO: 123, SEQ ED NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131 , SEQ ED NO: 133, SEQ ED NO: 135, SEQ JD NO: 137, SEQ ED NO: 139, SEQ ID NO: 141, SEQ JD NO: 143, SEQ ED NO: 145, SEQ ED NO: 147, SEQ JD NO: 149, SEQ ID NO: 151, SEQ ED NO: 153, SEQ ED NO: 155, SEQ ED NO: 157, SEQ ED NO: 159, SEQ ED NO: 161, SEQ ED NO: 163, or SEQ
ED NO: 165;
(d) the amino acid sequence of SEQ ED NO: 168, SEQ JD NO: 170, SEQ ED NO: 172, SEQ ID NO: 174, SEQ ED NO: 176, SEQ ED NO: 178, SEQ ID NO: 180, SEQ ED NO: 182, SEQ ED NO: 184, SEQ ED NO: 186, SEQ ED NO: 188, SEQ ED NO: 190, SEQ ID NO: 192, SEQ JD NO: 194, SEQ JD NO: 196, SEQ JD NO: 198, SEQ JD NO: 200, SEQ
HD NO: 202, SEQ ID NO: 204, SEQ HD NO: 206, SEQ ED NO: 208, SEQ ED NO: 210, SEQ ED NO: 212, SEQ ED NO: 214, or SEQ ED NO: 216, or SEQ JD NO: 218; or
(e) the amino acid sequence of SEQ ED NO: 221, SEQ JD NO: 223, SEQ ID NO: 225, SEQ ID NO: 227, SEQ JD NO: 229, SEQ ED NO: 231, SEQ JD NO: 233, SEQ HD NO: 235, SEQ ID NO: 237, SEQ JD NO: 239, SEQ ED NO: 241, SEQ ED NO: 243, SEQ
ED NO: 245, SEQ D NO: 247, SEQ ED NO: 249, SEQ ED NO: 251, SEQ ED NO: 253, SEQ
134
AMENDED SHEET {ARTICLE 19) ED NO: 255, SEQ ED NO: 257, SEQ ED NO: 259, SEQ ED NO: 261, SEQ ED NO: 263, SEQ ID NO: 265, or SEQ ED NO: 267.
60. A primer comprising an isolated nucleic acid molecule which hybridizes under highly stringent conditions to:
(a) the nucleic acid sequence of SEQ ED NO: 2, SEQ ED NO: 4, SEQ ED NO: 6, SEQ ED NO: 8, SEQ ED NO: 10, SEQ ED NO: 12, SEQ ED NO: 14, SEQ ED NO: 16, SEQ ED NO: 18, SEQ ID NO: 20, SEQ JD NO: 22, SEQ ID NO: 24, SEQ ED NO: 26, SEQ ED NO: 28, or SEQ ID NO: 30; (b) the nucleic acid sequence of SEQ ED NO: 33, SEQ ED NO: 35, SEQ ED
NO: 37, SEQ ED NO: 39, SEQ ED NO: 41, SEQ ED NO: 43, SEQ ED NO: 45, SEQ ED NO: 47, SEQ ED NO: 49, SEQ ED NO: 51, SEQ ED NO: SEQ ED NO: 53, or SEQ ED NO: 55;
(c) the nucleic acid sequence of SEQ ED NO: 58, SEQ JD NO: 60, SEQ ED NO: 62, SEQ JD NO: 64, SEQ JD NO: 66, SEQ ED NO: 68, SEQ ID NO: 70, SEQ ID NO: 72, SEQ ED NO: 74, SEQ ED NO: 76, SEQ ED NO: 78, SEQ ED NO: 80, SEQ JD NO: 82,
SEQ ED NO: 84, SEQ ID NO: 86, SEQ JD NO: 88, SEQ ID NO: 90, SEQ JD NO: 92, SEQ ID NO: 94, SEQ ED NO: 96, SEQ ED NO: 98, SEQ ED NO: 100, SEQ ED NO: 102, SEQ ID NO: 104, SEQ ID NO: 106, SEQ ID NO: 108 SEQ ED NO: 110, SEQ ID NO: 112, SEQ ED NO: 114, SEQ JD NO: 116, SEQ JD NO: 118, SEQ ID NO: 120, SEQ ID NO: 122, SEQ ID NO: 124, SEQ ED NO: 146, SEQ ID NO: 148, SEQ ED NO: 130, SEQ ID NO: 132, SEQ HD
NO: 134, SEQ ID NO: 136, SEQ JD NO: 138, SEQ ED NO: 140, SEQ ID NO: 142, SEQ ED NO: 144, SEQ JD NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ JD NO: 152, SEQ JD NO: 154, SEQ ED NO: 156, SEQ JD NO: 158, SEQ ED NO: 160, SEQ ID NO: 162, or SEQ ID NO: 164; (d) the nucleic acid sequence of SEQ ID NO: 167, SEQ JD NO: 169, SEQ
ID NO: 171, SEQ HD NO: 173, SEQ JD NO: 175, SEQ JD NO: 177, SEQ HD NO: 179, SEQ ID NO: 181, SEQ ID NO: 183, SEQ ID NO: 185, SEQ ID NO: 187, SEQ ID NO: 189, SEQ ID NO: 191, SEQ JD NO: 193, SEQ ED NO: 195, SEQ ED NO: 197, SEQ ED NO: 199, SEQ ED NO: 201, SEQ JD NO: 203, SEQ JD NO: 205, SEQ HD NO: 207, SEQ ID NO: 209, SEQ HD NO: 211, SEQ JD NO: 213, SEQ ED NO: 215, or SEQ ED NO: 217;
135 (e) the nucleic acid sequence of SEQ ED NO: 220, SEQ JD NO: 222, SEQ HD NO: 224, SEQ ED NO: 226, SEQ ED NO: 228, SEQ ED NO: 230, SEQ ED NO: 232, SEQ ED NO: 234, SEQ ED NO: 236, SEQ ED NO: 238, SEQ ED NO: 240, SEQ ED NO: 242, SEQ JD NO: 244, SEQ JD NO: 246, SEQ ED NO: 248, SEQ ED NO: 250, SEQ ED NO: 252, SEQ ED NO: 254, SEQ ED NO: 256, SEQ ED NO: 258, SEQ ED NO: 260, SEQ JD NO: 262, SEQ
ID NO: 264, or SEQ ED NO: 266; or
(f) the nucleic acid sequence of SEQ JD NO: 1 , SEQ JD NO: 32, SEQ ED NO: 57, SEQ ED NO: 166, or SEQ ED NO: 219.
61. A method for diagnosing a protective sequence-mediated condition, disorder or disease in an individual comprising obtaining a biological sample from said individual; contacting said biological sample with the primer according to claim 60; wherein if said primer interacts with said biological sample, but does not interact with a biological sample from a control individual not undergoing a protective sequence-mediated condition, disorder or disease, then a protective sequence-mediated condition, disorder or disease has been diagnosed.
62. A diagnostic kit for detecting a protective sequence-mediated condition, disorder or disease in an individual comprising a reagent in suitable packaging, wherein said reagent comprises the primer according to claim 60.
136
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