Methods and compositions for treating and diagnosing a SAGE1-related condition
AssigneesShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiaotong University School of Medicine
InventorsMing Lei, Wei Deng, Yanjie Zhang, Yang Song, Chao Zheng
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Abstract
The present disclosure provides methods and kits for diagnosing and assessing SAGE1-positive disorders, and compositions and methods for treating SAGE1-positive disorders. The present disclosure further provides SAGE1 complexes and methods and composition for inhibiting SAGE1 complexes and treating SAGE1-positive disorders.
Claims28
A method of diagnosing a SAGE1 positive disorder in a subject, comprising:
- (a) lysing cells from a biological sample of a subject to obtain a supernatant;
- (b) contacting the supernatant with an anti-SAGE1 antibody to immunoprecipitate proteins;
- (c) separating the proteins by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE);
- (d) visualizing the proteins by silver staining;
- and
- (e) detecting INTS3 within the proteins by Mass Spectrometry (MS);
- wherein when INTS3 is detected, a SAGE1-INTS3 complex is identified in the biological sample, indicating a SAGE1 expression is detected in the biological sample, and the subject is diagnosed as having a SAGE1 positive disorder.
A method of assessing malignancy or malignancy potential of a tumor in a subject, comprising:
- (a) lysing cells from a biological sample of a subject to obtain a supernatant;
- (b) contacting the supernatant with an anti-SAGE1 antibody to immunoprecipitate proteins;
- (c) separating the proteins by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis;
- (d) visualizing the proteins by silver staining;
- and
- (e) detecting INTS3 within the proteins by Mass Spectrometry;
- wherein when INTS3 is detected, a SAGE1-INTS3 complex is identified in the biological sample, indicating a SAGE1 expression is detected in the biological sample, and the tumor is assessed to be malignant or as having malignancy potential.
A SAGE1 inhibitor, comprising an oligonucleotide targeting SAGE1 nucleic acid, or a polynucleotide encoding the oligonucleotide, or a nucleic acid vector comprising the oligonucleotide or the polynucleotide;
- wherein the oligonucleotide comprises a sequence selected from SEQ ID NOs:
- 82-95, and 106-147, or the oligonucleotide comprises a pair of sense/antisense sequences selected from SEQ ID NOs:
- 70/71, 72/73, 74/75, 76/77, 78/79, and 80/81.
A method of treating or alleviating one or more symptoms of a SAGE1 positive disorder in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a SAGE1 inhibitor, wherein the inhibitor comprises (a) a SAGE1-binding fragment of INTS3 comprising an amino acid sequence of SEQ ID NO:
- 9;
- (b) an INTS3-binding fragment of SAGE1 comprising an amino acid sequence of SEQ ID NO:
- 8;
- or (c) an INTS3-binding fragment of INTS6 or INTS6L comprising an amino acid sequence of SEQ ID NO:
- 10, SEQ ID NO:
- 104, or SEQ ID NO:
- 105.
A method of determining sensitivity of a tumor sample to a SAGE1 inhibitor, comprising:
- (a) lysing cells from the tumor sample of a subject to obtain a supernatant;
- (b) contacting the supernatant with an anti-SAGE1 antibody to immunoprecipitate proteins;
- (c) separating the proteins by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis;
- (d) visualizing the proteins by silver staining;
- and
- (e) detecting INTS3 within the proteins by Mass Spectrometry;
- wherein when INTS3 is detected, a SAGE1-INTS3 complex is identified in the tumor sample, indicating a SAGE1 expression is detected in the tumor sample, and the tumor sample is determined to be sensitive to the SAGE1 inhibitor.
A method of identifying a subject having a tumor who is likely to benefit from treatment with a SAGE1 inhibitor, comprising:
- (a) lysing cells from a tumor sample of a subject to obtain a supernatant;
- (b) contacting the supernatant with an anti-SAGE1 antibody to immunoprecipitate proteins;
- (c) separating the proteins by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis;
- (d) visualizing the proteins by silver staining;
- and
- (e) detecting INTS3 within the proteins by Mass Spectrometry;
- wherein when INTS3 is detected, a SAGE1-INTS3 complex is identified in the tumor sample, indicating a SAGE1 expression is detected in the tumor sample, and the subject is identified as being likely to benefit from treatment with the SAGE1 inhibitor.
A method of monitoring progression of a SAGE1 positive disorder in a subject, comprising:
- (a) lysing cells from a first biological sample and a second biological sample of a subject to obtain a first supernatant and a second supernatant, respectively;
- wherein the second biological sample is obtained after a course of time from the first sample;
- (b) contacting the first and the second supernatants with an anti-SAGE1 antibody to immunoprecipitate a first protein in the first supernatant and a second protein in the second supernatant;
- (c) separating the first and second proteins by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis;
- (d) visualizing the first and second proteins by silver staining;
- (e) detecting INTS3 within the first and second proteins by Mass Spectrometry;
- if INTS3 in the first and second proteins is detected, a SAGE1-INTS3 complex is identified in the first and second biological samples, indicating a SAGE1 expression is detected in the first and second biological samples;
- and
- (f) measuring an amount of binding between the SAGE1 antibody and the first and second proteins to determine a level of SAGE1 expression in the first and second biological samples by using western blot;
- wherein when the level of SAGE1 expression in the second biological sample is higher than that in the first biological sample, the SAGE1 positive disorder is determined as having progressed.
Dependencies are inferred from the claim text.