ATP-binding cassette family coding polyribonucleotides and formulations thereof
Inventors
Plank, Christian • Rudolph, Carsten • Aneja, Manish Kumar • Weiss, Ludwig • Ferizi, Mehrije • GEIGER, Johannes
Assignees
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Publication Number
US-11479768-B2
Publication Date
2022-10-25
Expiration Date
Abstract
Polynucleotides encoding peptides, proteins, enzymes, and functional fragments thereof are disclosed. The polynucleotides of the disclosure can be effectively delivered to an organ, such as the lung, and expressed within cells of the organ. The polyribonucleotides of the disclosure can be used to treat a disease or condition associated with a gene of the ATP-binding cassette (ABC) family, such as ABCA3.
Core Innovation
The invention provides modified polyribonucleotides that include an untranslated region derived from a cytochrome b-245 alpha polypeptide gene. The untranslated region comprises a 5′ untranslated region comprising SEQ ID NO: 14 or a sequence having 1 to 4 substitutions compared to SEQ ID NO: 14 and/or a 3′ untranslated region comprising SEQ ID NO: 15 or a sequence having 1 to 7 substitutions compared to SEQ ID NO: 15. Upon translation, the modified polyribonucleotide yields an ABCA3 protein, a functional fragment thereof, or a functional homolog thereof.
The invention relates to sequences and RNA modifications intended to optimize translation efficiency and reduce inflammation and immunogenicity. The disclosure includes modified RNA using uridine, cytidine, adenosine, and guanosine analogues to influence immune response and inflammatory markers.
The invention further provides compositions and delivery approaches for the modified polyribonucleotides, including formulation with nanoparticles or nanoparticle/nanocapsule formats and delivery using cationic lipid, cationic polymers, or nanoemulsions.
Claims Coverage
The provided materials identify one independent claim directed to a composition comprising a modified polyribonucleotide with cytochrome b-245 alpha-derived 5′ and/or 3′ untranslated regions specified by SEQ ID NO: 14 and SEQ ID NO: 15, allowing limited substitutions, that yields ABCA3 protein, a functional fragment, or a functional homolog upon translation. Dependent claims refine the inventive concept by adding nucleotide analogue constraints, specific analogue identities, formulation formats, and administration-based treatment context.
Cytochrome b-245 alpha untranslated region-defined ABCA3-yielding modified polyribonucleotide composition
A composition comprising a modified polyribonucleotide with an untranslated region derived from a cytochrome b-245 alpha polypeptide gene, where the untranslated region comprises a 5′ untranslated region comprising SEQ ID NO: 14 or a sequence having 1 to 4 substitutions versus SEQ ID NO: 14 and/or a 3′ untranslated region comprising SEQ ID NO: 15 or a sequence having 1 to 7 substitutions versus SEQ ID NO: 15, such that upon translation the modified polyribonucleotide yields an ABCA3 protein, a functional fragment thereof, or a functional homolog thereof.
Limited analogue content for adenosine or guanosine
The modified polyribonucleotide contains less than 50% analogues of adenosine or guanosine.
Uridine or cytidine analogue proportion constraints
The modified polyribonucleotide contains 15% to 30% uridine analogues and/or 15% to 30% cytidine analogues.
Specific nucleotide analogue identities
The modified polyribonucleotide includes 5-methylcytidine or pseudouridine.
Nanoparticle or nanoemulsion formulation
The modified polyribonucleotide composition is formulated in a nanoparticle/nanocapsule or in a cationic lipid, cationic polymer, or nanoemulsion.
Treatment of disease or condition linked to an ABCA3 defect or eye malfunction
A method for treating a disease or condition linked to an ABCA3 defect or malfunction of the eye by administering the composition to a subject in need.
The claim coverage centers on a modified polyribonucleotide defined by cytochrome b-245 alpha untranslated regions and limited substitutions, with dependent features addressing nucleotide analogue composition, formulation, and administration-based treatment context.
Stated Advantages
Optimize translation efficiency.
Reduce inflammation and immunogenicity.
Reduce immune response and inflammatory markers.
Documented Applications
Treating a disease or condition linked to an ABCA3 defect by administering the composition to a subject in need.
Treating eye malfunction by administering the composition to a subject in need.
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