Methods for cascade amplifications of therapeutic payloads (catp) & compositions for cancer immunotherapies and gene therapy
AssigneeSunVax mRNA Therapeutics Inc.
InventorsYingzhong LI, Libin ZHANG
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Abstract
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of oncolytic defective virus compositions and methods of in vivo synthesis thereof. The composition includes a first nucleic acid construct encoding a self-amplifying mRNA (sa-mRNA) encoding at least one gene of interest (GOI) or a plurality of GOIs, a second nucleic acid construct encoding an mRNA encoding at least one virus structural protein, and at least one payload delivery system.
Claims30
A composition for cascade amplifications of therapeutic payloads (CATP) comprising:
- a) a first type nucleic acid construct encoding a self-amplifying mRNA (sa-mRNA) or multiple self-amplifying mRNA (sa-mRNA) encoding at least one gene of interest (GOI) or a plurality of GOIs;
- b) a second type nucleic acid construct encoding an mRNA encoding at least one virus structural protein;
- and
- c) at least one payload delivery system,
- wherein the at least one payload delivery system is a non-viral payload delivery system and wherein the payload is at least one nucleic acid construct.
A method of producing a mRNA comprising:
- a) contacting cells with a nucleic acid template encoding two expression units, the nucleic acid template comprising:
- i) an origin of replication sequence (Ori);
- ii) a first expression unit encoding a first nucleotide sequence that is operably linked to a first promoter;
- and
- iii) a second expression unit encoding a second nucleotide sequence that is operably linked to a second promoter,
- wherein the first expression unit encodes a selectable marker and the second expression unit encodes a mRNA;
- b) selecting cells that express the selectable marker;
- c) subculturing the selected cells to obtain a population of cells that express the selectable marker;
- d) propagating the population of cells to increase the copy number of nucleic acid template replicates comprising the second expression unit encoding the mRNA;
- and
- e) cleaving the nucleic acid template replicates between the first expression unit and the second expression unit to produce the mRNA.
A nucleic acid molecule comprising any one or combination of SEQ ID NOs in Table 16.
A method of treating a subject having a tumor or cancer, comprising administering to a subject a composition comprising an IL-12 and an IL-18 or IL-12 and an mutant IL-18.
Dependencies are inferred from the claim text.