Compositions comprising circular polyribonucleotides and uses thereof
AssigneeFlagship Pioneering Innovations VI, LLC
InventorsAlexandra Sophie DE BOER, Avak KAHVEJIAN, Nicholas McCartney PLUGIS, Erica Gabrielle WEINSTEIN, Sebastian TROUSIL, Morag Helen STEWART, Ki Young PAEK, Catherine CIFUENTES-ROJAS
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Abstract
This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.
Claims30
A pharmaceutical composition for persistent expression of a therapeutic polypeptide, comprising:
- a pharmaceutically acceptable excipient;
- and
- a covalently closed polyribonucleotide that (a) persistently expresses the therapeutic polypeptide for at least 7 days in a mammalian subject after the pharmaceutical composition is administered to the mammalian subject, and (b) comprises:
- (i) an internal ribosome entry site (IRES) element;
- (ii) an expression sequence that encodes the therapeutic polypeptide, and lacks either a 5′ cap or a 3′ poly-A sequence, and (iii) a termination element.
A pharmaceutical composition for persistent expression of a therapeutic polypeptide, comprising:
- a pharmaceutically acceptable excipient;
- and
- a covalently closed polyribonucleotide that (a) persistently expresses the therapeutic polypeptide for at least 7 days in a mammalian subject after the pharmaceutical composition is administered to the mammalian subject, and (b) comprises:
- (i) an internal ribosome entry site (IRES) element;
- (ii) an expression sequence that encodes the therapeutic polypeptide, and lacks a 5′ cap and a 3′ poly-A sequence, and (iii) a termination element,
- wherein the therapeutic polypeptide is selected from the group consisting of an antigen, at least a functional portion of a viral envelope protein, a hormone, a cytokine, a ligand, a receptor, an antibody, an enzyme, a secreted protein, an epigenetic modifying agent, a nuclease, a component of a CRISPR system, a pore forming peptide, a cytotoxic peptide, and an anti-microbial peptide.
A pharmaceutical composition comprising a covalently closed RNA encoding a therapeutic polypeptide, wherein the pharmaceutical composition is produced by a method comprising:
- (a) providing a non-coding RNA;
- (b) engineering the non-coding RNA (i) to produce a translation-competent RNA and (ii) to add a coding sequence for a therapeutic polypeptide operably linked to a promoter;
- (c) covalently joining a first portion and a second portion of the translation-competent RNA produced in step (b) to produce a translation-competent, covalently closed RNA encoding the therapeutic polypeptide;
- (d) purifying the translation-competent, covalently closed RNA encoding the therapeutic polypeptide produced in step (c);
- and
- (e) formulating the purified translation-competent, covalently closed RNA encoding the therapeutic polypeptide produced in step (d) with a pharmaceutical excipient to produce a pharmaceutical composition;
- wherein the pharmaceutical composition, when administered to a mammalian subject, expresses the therapeutic polypeptide in vivo for at least 7 days.
Dependencies are inferred from the claim text.