Loading patent…
AssigneeModernaTX, Inc.
InventorsPaolo Martini, Vladimir Presnyak, Jingsong CAO
Estimating the term…
The present disclosure provides compositions of nucleic acids relating to biliary epithelial transporters. For example, the present disclosure relates to nucleic acids capable of regulating the biliary secretion of phospholipids, including phosphatidylcholine, e.g., those encoded by ATP binding cassette subfamily B member 4 (ABCB4) or a biologically active fragment thereof, in a target cell. In a preferred embodiment, the present disclosure provides compositions comprising modified mRNA encoding ABCB4 formulated in a lipid nanoparticle (LNP) carrier and derivative constructs, which are useful for treating or preventing progressive familial intrahepatic cholestasis type 3 (PFIC3).
A composition comprising a modified polynucleotide having an open reading frame (ORF) encoding ATP binding cassette subfamily B member 4 (ABCB4) formulated in a lipid nanoparticle (LNP) carrier.
The composition of any of the preceding claims, wherein the modified polynucleotide comprises a poly-A region, a Kozak sequence, a 3′ untranslated region, a 5′ untranslated region, an miRNA binding site, or any combination thereof.
The composition of any one of the preceding claims, wherein the ORF further comprises at least one low-frequency codon.
The composition of any one of the preceding claims, wherein the ORF is
The composition of any one of the preceding claims, wherein the LNP comprises an ionizable amino lipid.
A polynucleotide comprising an ORF,
The composition of any one of the preceding claims, wherein the ABCB4 polypeptide comprises an amino acid sequence at least about 95% identical to (a) the polypeptide sequence of wild type ABCB4, isoform 1, (b) the polypeptide sequence of wild type ABCB4, isoform 2, or (c) the polypeptide sequence of wild type ABCB4, isoform 3, wherein the ABCB4 polypeptide has phosphatidylcholine translocation activity.
The composition of any one of the preceding claims, wherein the polynucleotide encodes an ABCB4 polypeptide fused to one or more heterologous polypeptides.
The composition of any one of the preceding claims, wherein, upon administration to a subject, the polynucleotide has:
A method of producing a polynucleotide having an open reading frame (ORF) encoding ATP binding cassette subfamily B member 4 (ABCB4), comprising modifying an ORF encoding an ABCB4 polypeptide by performing at least one synonymous substitution.
A method of treating or preventing progressive familial intrahepatic choleostasis type 3 (PFIC3) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a composition comprising a modified mRNA molecule encoding an ABCB4 polypeptide.
A method of treating PFIC2 or BRIC2 in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a composition comprising a modified mRNA encoding a BSEP polypeptide.
A method of treating PFIC1 in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a composition comprising a modified mRNA encoding ATP8B1.
A composition comprising a modified mRNA molecule encoding an ABCB4 polypeptide for use in a method of treating or preventing progressive familial intrahepatic choleostasis type 3 (PFIC3).
A composition comprising a modified mRNA encoding a BSEP polypeptide for use in a method of treating PFIC2 or BRIC2.
A composition comprising a modified mRNA encoding ATP8B1 for use in a method of treating PFIC1.
Dependencies are inferred from the claim text.