Methods and compositions for targeting serine dehydratase
OwnerChristian Metallo, Prashant Mali +4inventors
InventorsChristian Metallo, Prashant Mali, Emeline Joulia, Joseph Rainaldi, Patrick Tseng, Ethan Ashley
Life of this patent
Estimating the term…
Abstract
Disclosed herein are methods and compositions for increasing serine levels, increasing ceramide levels, and/or decreasing deoxyceramide, such as deoxydihydroceramide, levels in one or more tissues in a subject in need thereof. In particular, the technology of the present disclosure relates to biological approaches for disrupting serine hydratase (SDS) activity in a subject.
Claims29
A method for increasing serine levels in one or more tissues in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent that disrupts serine dehydratase (SDS) activity, wherein the agent is selected from the group consisting of:
- an antisense oligonucleotide, a shRNA, a siRNA, a zinc finger nuclease, and CRISPR-Cas system.
(canceled)
-7. (canceled)
(canceled)
(canceled)
-22. (canceled)
A composition comprising an agent the disrupts serine dehydratase (SDS) activity, wherein the agent is selected from the group consisting of:
- (a) an antisense oligonucleotide, or a nucleic acid encoding the same, comprising a nucleotide sequence selected from any one of the oligonucleotides as set forth in Table 12 or Table 13;
- (b) a siRNA, or a nucleic acid encoding the same, comprising a nucleotide sequence selected from any one of the oligonucleotides as set forth in Table 12 or Table 13;
- (c) a shRNA, or a nucleic acid encoding the same, comprising a nucleotide sequence selected from any one of the oligonucleotides as set forth in SEQ ID NOs:
- 2-6, Table 12, or Table 13;
- (d) a zinc finger peptide, or a nucleic acid encoding the same, as set forth in Table 1, Table, 2, Table 3, Table 4, or Table 5;
- and
- (e) a nucleic acid encoding a CRISPR-Cas system, wherein the nucleic acid encodes a guide RNA comprising the oligonucleotide selected from any one of the oligonucleotides as set forth in Table 6, Table 7, Table 8, Table 9, Table 10, or Table 11.
-31. (canceled)
A method for increasing ceramide levels and/or decreasing deoxyceramide levels in one or more tissues in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent that disrupts serine dehydratase (SDS) activity, wherein the agent is selected from the group consisting of:
- an antisense oligonucleotide, a shRNA, a siRNA, a zinc finger, and a nucleic acid encoding a CRISPR-Cas system.
-40. (canceled)
A method for selecting a subject for treatment with a therapeutically effective amount of an agent that disrupts serine dehydratase (SDS) activity, the method comprising:
- (a) detecting levels of serine in a blood sample from the subject;
- (b) selecting the subject for treatment with the agent that disrupts SDS activity where the level of serine and/or glycine in the blood sample from the subject is reduced by about 20% compared to the normal control sample;
- and
- (c) administering to the subject a therapeutically effective amount of the agent that disrupts SDS activity, wherein the agent is selected from the group consisting of:
- an antisense oligonucleotide, a shRNA, a siRNA, a zinc finger nuclease, and CRISPR-Cas system.
-45. (canceled)
A method for treating diabetes, treating diabetic peripheral neuropathy, treating obesity, or treating one or more wounds in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent that disrupts serine dehydratase (SDS) activity, wherein the agent is selected from the group consisting of:
- an antisense oligonucleotide, a shRNA, a siRNA, a zinc finger nuclease, and CRISPR-Cas system.
-64. (canceled)
Dependencies are inferred from the claim text.