MicroRNA-33 inhibitors and use thereof in the treatment of pulmonary fibrosis
Inventors
AHANGARI, Farida • Kaminski, Naftali • Fernandez-Hernando, Carlos • Bahal, Raman
Assignees
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Publication Number
US-12060555-B2
Publication Date
2024-08-13
Expiration Date
Abstract
In one aspect, the present disclosure provides a microRNA-33 (miR-33) inhibitor comprising a peptide nucleic acid covalently bound to a pH low insertion peptide. In another aspect, the present disclosure provides a method of treating pulmonary fibrosis in a subject, the method comprising administering to the subject a therapeutically effective amount of the miR-33 inhibitor. In some embodiments, the pulmonary fibrosis is idiopathic pulmonary fibrosis.
Core Innovation
The disclosed invention relates to a method of treating, ameliorating, or reducing pulmonary fibrosis in a subject in need thereof by administering a microRNA-33 (miR-33) inhibitor. The miR-33 inhibitor is an antisense peptide nucleic acid (PNA) that comprises a nucleobase sequence set forth in SEQ ID NO:1 or SEQ ID NO:2.
In embodiments, the antisense PNA is defined by a formula (I) with parameter constraints including m, n, q, and p, where m, n, and q are each integers from 1 to 3 and p is an integer in a specified range. The disclosure also includes embodiments in which the PNA is linked or covalently bound to a pH low insertion peptide (pHLIP), forming a PNA-pHLIP conjugate.
The background rationale disclosed is that miR-33 is increased in idiopathic pulmonary fibrosis (IPF), including in BAL cells/macrophages. The disclosure further provides that miR-33 ablation, including global or macrophage-specific miR-33 knockout, protects against bleomycin-induced pulmonary fibrosis.
Claims Coverage
The document includes one independent claim directed to a method of treating pulmonary fibrosis with a miR-33 inhibitor, plus dependent claims that refine the miR-33 inhibitor composition and delivery. The independent claim is supported by inventive features focusing on miR-33 inhibition using a PNA defined by specific SEQ ID sequences and administration via specified routes.
Treating pulmonary fibrosis with miR-33 inhibitor administration
A method of treating, ameliorating, or reducing pulmonary fibrosis by administering to the subject a therapeutically effective amount of a microRNA-33 (miR-33) inhibitor via a mode of administration selected from nasal, pulmonary, aerosol, inhalational, intratracheal, intrabronchial, intraperitoneal, intravenous, and oral gavage.
Antisense PNA using defined SEQ ID sequences
The miR-33 inhibitor is an antisense peptide nucleic acid (PNA) comprising a nucleobase sequence set forth in SEQ ID NO:1 or SEQ ID NO:2.
Across the claims coverage provided, the inventive scope is centered on delivering a therapeutically effective miR-33 inhibitor for pulmonary fibrosis using an antisense PNA with the specified SEQ ID NO:1 or SEQ ID NO:2 sequences, with delivery selectable among multiple administration routes.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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