Compositions useful in treatment of ornithine transcarbamylase (OTC) deficiency
AssigneeThe Trustees of the University of Pennsylvania
InventorsLili Wang, James M. Wilson
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Abstract
Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis cirrhosis in OTCD patients by administering hOTC.
Claims27
A recombinant viral vector comprising a nucleic acid sequence encoding human ornithine transcarbamylase (hOTC) and expression control sequences which direct expression of hOTC in a liver cell, wherein the hOTC nucleic acid sequence is less than 80% identical to the wild-type hOTC sequence over the mature sequence or full length hOTC of SEQ ID NO:
- 1, and expresses a functional hOTC, wherein said hOTC nucleic acid sequence is SEQ ID NO:
- 5 or a nucleic acid sequence at least 96 to 99% identical thereto.
A recombinant adeno-associated virus (rAAV) having an AAV capsid and packaged therein an expression cassette comprising at least one AAV ITR sequence, an engineered nucleic acid sequence encoding hOTC, and expression control sequences which direct expression of the hOTC in a liver cell, said expression control sequences comprising a liver-specific promoter, wherein the hOTC nucleic acid sequence is SEQ ID NO:
- 5 or a nucleic acid sequence at least 96 to 99.9% identical thereto and expresses a functional hOTC.
A viral vector comprising a hOTC gene encoding a chimeric ornithine Transcarbamylase which comprises at least mature hOTC with a heterologous transit sequence, wherein the coding sequence of the mature hOTC is selected from a nucleic acid sequence of SEQ ID NO:
- 4, or 5.
Dependencies are inferred from the claim text.