Pharmaceutical composition for diagnosing, preventing or treating liver cancer using SSU72 protein or a polynucleotide encoding the same
Inventors
Lee, Chang Woo • LEE, Jin Kwan • Kim, Hyun Soo • Kim, Jae-Kyung • YOON, Joon Sup
Assignees
Curogen Technology Co Ltd • Research ＆ Business Foundation Sungkyunkwan University • Sungkyunkwan University
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Publication Number
US-11918632-B2
Publication Date
2024-03-05
Expiration Date
Abstract
The present invention provides a method for preventing or treating liver cancer in a subject comprising administrating at least one selected from the group consisting of an Ssu72 peptide, a polynucleotide encoding the Ssu72 peptide and an expression vector containing the polynucleotide to the subject.
Core Innovation
A method is disclosed for treating a patient suffering from liver cancer by administering an adeno-associated virus (AAV) vector comprising a polynucleotide encoding a Ssu72 peptide and a liver-specific promoter operably linked to the polynucleotide. The AAV vector is administered by systemic administration or an intrahepatic administration, and embodiments include an AAV8 vector.
The liver-specific promoter is selected from thyroxin-binding globulin (TBG), PBGD, α-1 anti-trypsin (EhAlbAAT), Hepatic Control Region (HCR)-based hybrid promoters (HCR-ApoCII and HCR-hAAT), apolipoprotein E (ApoE), phosphoglycerate kinase (PGK), or a hybrid liver-specific promoter (HLP). In an embodiment, the TBG promoter comprises SEQ ID NO: 3, and the Ssu72 peptide and encoding polynucleotide are specified by SEQ ID NO: 1 and SEQ ID NO: 2.
A diagnostic and predictive approach is also disclosed that involves reducing Ssu72 expression or Ssu72 activity to identify NASH-derived HCC. Mechanistic disclosure indicates an interaction between Ssu72 and HNF4α, affecting HNF4α phosphorylation and/or activity, including phosphorylated HNF4α (Ser304/pS304).
Claims Coverage
The provided set contains one independent claim covering treating liver cancer with a systemically or intrahepatically administered AAV vector encoding Ssu72 under control of a liver-specific promoter. Across the dependent claims, multiple inventive-feature refinements are specified, including Ssu72 sequence identity, polynucleotide sequence identity, selection of AAV subtype, and selection of specific liver-specific promoter configurations including TBG promoter sequence specification.
AAV vector encoding Ssu72 under liver-specific promoter
Administering to the patient an adeno-associated virus (AAV) vector comprising a polynucleotide encoding a Ssu72 peptide and a liver-specific promoter operably linked to the polynucleotide.
Systemic or intrahepatic administration of the AAV vector
Administering the AAV vector by systemic administration or an intrahepatic administration.
AAV8 vector
The AAV vector is an AAV8 vector.
Ssu72 peptide as SEQ ID NO: 1
The Ssu72 peptide comprises the amino acid sequence specified as SEQ ID NO: 1.
Ssu72-encoding polynucleotide as SEQ ID NO: 2
The Ssu72 peptide is encoded by a polynucleotide with the nucleotide sequence of SEQ ID NO: 2.
Liver-specific promoter selected from specified promoter types
The liver-specific promoter is selected from thyroxin-binding globulin (TBG), PBGD, α-1 anti-trypsin (EhAlbAAT), Hepatic Control Region (HCR)-ApoCII hybrid promoter, HCR-hAAT hybrid promoter, apolipoprotein E (ApoE), phosphoglycerate kinase (PGK), or a hybrid liver-specific promoter (HLP).
TBG promoter comprising SEQ ID NO: 3
The TBG promoter comprises SEQ ID NO: 3.
Overall claim coverage centers on treating liver cancer by delivering a Ssu72-encoding polynucleotide within an AAV vector under control of a liver-specific promoter, with delivery by systemic or intrahepatic administration. Dependent features further narrow the configuration by specifying an AAV8 vector embodiment, defining the Ssu72 peptide and its encoding polynucleotide sequences (SEQ ID NO: 1 and SEQ ID NO: 2), and selecting among multiple liver-specific promoters including a TBG promoter embodiment specified by SEQ ID NO: 3.
Stated Advantages
Documented Applications
No documented applications found
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