Modulation of SPTLC1 via recombinant adeno-associated vectors
AssigneeUniversity of Massachusetts
InventorsChristian Mueller, Gabriela Toro Cabrera, Robert H. Brown, Jr.
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Abstract
The disclosure provides, in some aspects, compositions (e.g., isolated nucleic acids and rAAVs) comprising a transgene which encodes at least one inhibitory nucleic acid which decreases expression of a gene encoding a serine palmitoyltransferase protein (e.g., SPTLC1). In some aspects, the disclosure relates to methods of treating hereditary sensory and autonomic neuropathy 1 (HSAN1) by administering the compositions described by the disclosure to a cell or subject.
Claims9
An isolated nucleic acid comprising a transgene encoding at least one inhibitory nucleic acid, wherein the at least one inhibitory nucleic acid comprises a nucleic acid sequence that is complementary to a nucleic acid encoding a serine palmitoyltransferase subunit, wherein the transgene is flanked by inverted terminal repeats (ITRs) derived from adeno-associated virus (AAV), wherein the at least one inhibitory nucleic acid is a microRNA (miRNA) or an artificial microRNA (amiRNA), and wherein the at least one inhibitory nucleic acid comprises:
- (i) a first strand comprising SEQ ID NO:
- 16 and a second strand comprising SEQ ID NO:
- 17;
- (ii) a first strand comprising SEQ ID NO:
- 18 and a second strand comprising SEQ ID NO:
- 19;
- or
- (iii) a first strand comprising SEQ ID NO:
- 20 and a second strand comprising SEQ ID NO:
- 21.
A recombinant AAV (rAAV) comprising:
- (i) an isolated nucleic acid comprising a transgene encoding an inhibitory nucleic acid, wherein the inhibitory nucleic acid comprises a nucleic acid sequence that is complementary to a nucleic acid sequence encoding a serine palmitoyltransferase subunit, wherein the transgene is flanked by inverted terminal repeats (ITRs) derived from adeno-associated virus (AAV), wherein the inhibitory nucleic acid is a microRNA (miRNA) or an artificial microRNA (amiRNA), and wherein the inhibitory nucleic acid comprises:
- a first strand comprising SEQ ID NO:
- 16 and a second strand comprising SEQ ID NO:
- 17;
- a first strand comprising SEQ ID NO:
- 18 and a second strand comprising SEQ ID NO:
- 19;
- or
- a first strand comprising SEQ ID NO:
- 20 and a second strand comprising SEQ ID NO:
- 21;
- and
- (ii) at least one capsid protein.
Dependencies are inferred from the claim text.