Chimeric nucleic acid molecules with non-aug translation initiation sequences and uses thereof
AssigneeMarker Therapeutics, Inc.
InventorRobert Z. Florkiewicz
Life of this patent
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Abstract
The present disclosure relates to nucleic acid vaccine compositions and methods for preventing or treating pathological conditions, such as cancer or infectious disease. Further, the disclosure provides methods for more efficient production of antigens via mRNA containing one or more non-conventional start codons to promote multiplex initiation of translation in eukaryotic cells.
Claims24
-30. (canceled)
A T cell comprising a chimeric nucleic acid molecule comprising a multiplex translation initiation (MTI) sequence comprising from two to about five translation initiation sites operatively linked in frame to a nucleic acid molecule encoding a polypeptide comprising one or more cytokine, wherein at least one of the MTI translation initiation sites is a non-AUG translation initiation site and the MTI allows the production of more than one mole of polypeptide per mole of mRNA,
- wherein the chimeric nucleic acid molecule is an mRNA molecule or an mRNA molecule contained in a vector and operably linked to an expression control sequence.
A T cell comprising a multiplex translation initiation (MTI) sequence-comprising a 5′-portion of a human FGF2 gene, wherein the 5′-portion of the human FGF2 gene comprises (i) an AUG translation initiation site and (ii) a sequence comprising from about 123 nucleotides to about 385 nucleotides upstream of the AUG translation initiation site, wherein the sequence upstream of the AUG translation initiation site comprises one to four translationally active non-AUG translation initiation sites in frame with the AUG translation initiation site, wherein the MTI is operatively linked in frame to a nucleic acid molecule encoding a polypeptide comprising one or more cytokine and the MTI allows the production of more than one mole of polypeptide per mole of mRNA,
- wherein the chimeric nucleic acid molecule is an mRNA molecule or an mRNA molecule contained in a vector and operably linked to an expression control sequence.
A method comprising introducing, into T cells from a subject, mRNA comprising a multiplex translation initiation (MTI) sequence comprising from two to about five translation initiation sites operatively linked in frame to a nucleic acid molecule encoding a polypeptide comprising one or more cytokine, wherein at least one of the MTI translation initiation sites is a non-AUG translation initiation site and the MTI allows the production of more than one mole of polypeptide per mole of mRNA.
Dependencies are inferred from the claim text.