Multi-terminus polya polynucleotides
OwnerMuthiah MANOHARAN, Chong WANG +1inventors
InventorsMuthiah MANOHARAN, Chong WANG, Anilkumar KORE
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Abstract
Provided herein are modified polynucleotides useful for increasing the stability of an mRNA molecule and/or production of a therapeutic protein.
Claims22
A multi-terminus polynucleotide comprising a first polyA polynucleotide linked to a second polyA polynucleotide, wherein the multi-terminus polyA polynucleotide comprises a formula represented by the structure:
- wherein:
- (X) is a first functionalized nucleotide within the first polyA polynucleotide, wherein the functionalized nucleotide comprises an amino modification, an alkoxyamino modification, a thiol modification, a carboxyl modification, or an aldehyde modification;
- (L) is a linker;
- (Y) is a second functionalized nucleotide within the second polyA polynucleotide, wherein the functionalized nucleotide comprises an amino modification, an alkoxyamino modification, a carboxyl modification, or an aldehyde modification;
- first functionalized nucleotide is linked to the linker through a linkage comprising an amide linkage, an oxime linkage, or a thioether linkage;
- and
- the linker is linked to the second functionalized nucleotide is linked to the linker through a linkage comprising an amide linkage, an oxime linkage, or a thioether linkage.
The multi-terminus polynucleotide claim of 1, wherein (X) is located at a non-terminal position of the first polyA polynucleotide.
A modified ribonucleic acid molecule comprising, 5′ to 3, a 5′ cap, a region encoding a polypeptide, and a multi-terminus polyA polynucleotide comprising a first polyA polynucleotide linked to a second polyA polynucleotide, wherein the multi-terminus polyA polynucleotide comprises a formula represented by the structure:
- wherein:
- (X) is a first functionalized nucleotide within the first polyA polynucleotide, wherein the functionalized nucleotide comprises an amino modification, an alkoxyamino modification, a thiol modification, a carboxyl modification, or an aldehyde modification;
- (L) is a linker;
- (Y) is a second functionalized nucleotide within the second polyA polynucleotide, wherein the functionalized nucleotide comprises an amino modification, an alkoxyamino modification, a carboxyl modification, or an aldehyde modification;
- first functionalized nucleotide is linked to the linker through a linkage comprising an amide linkage, an oxime linkage, or a thioether linkage;
- and
- the linker is linked to the second functionalized nucleotide is linked to the linker through a linkage comprising an amide linkage, an oxime linkage, or a thioether linkage.
A multi-terminus polynucleotide comprising a first polyA polynucleotide linked to a second polyA polynucleotide, wherein the multi-terminus polyA polynucleotide comprises a formula represented by the structure:
- wherein:
- (X) is a first functionalized nucleotide within the first polyA polynucleotide;
- (L) is a heteroalkyl linker;
- (Y) is a second functionalized nucleotide at the 3′ position of a second polyA polynucleotide;
- each (p) is independently an inter-nucleoside linkage or terminal phosphate or phosphorothioate;
- each (N) is independently a nucleotide or a modified nucleotide;
- each (n) is independently an integer equal to or greater than 1;
- the first functionalized nucleotide is linked to the linker;
- and
- the linker is linked to the second functionalized nucleotide.
A method of increasing translation of a polypeptide, the method comprising:
- contacting a cell with (i) a messenger ribonucleic acid molecule comprising the multi-terminus polynucleotide of acclaim 1.
A composition comprising modified ribonucleic acid molecule comprising, 5′ to 3, a 5′ cap, a region encoding a polypeptide, and a multi-terminus polyA polynucleotide comprising a first polyA polynucleotide linked to a second polyA polynucleotide, wherein the multi-terminus polyA polynucleotide comprises a formula represented by the structure:
- wherein:
- (X) is a first functionalized nucleotide within the first polyA polynucleotide;
- (L) is a heteroalkyl linker;
- (Y) is a second functionalized nucleotide at the 3′ position of a second polyA polynucleotide;
- each (p) is independently an inter-nucleoside linkage or terminal phosphate or phosphorothioate;
- each (N) is independently a nucleotide or a modified nucleotide;
- each (n) is independently an integer equal to or greater than 1;
- the first functionalized nucleotide is linked to the linker;
- the linker is linked to the second functionalized nucleotide;
- and
- the composition is substantially free of copper.
The composition of claim 21 or claim 22, wherein the composition is substantially free of copper trace copper.
Dependencies are inferred from the claim text.