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US 2026/0035707 A1Published application
Engineered polynucleotides for temporal control of expression
AssigneeModernaTX, Inc.
InventorRuchi Jain
Life of this patent
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Abstract
The disclosure features compositions, systems, and uses thereof, comprising polynucleotide(s) encoding target molecule(s), and polynucleotide(s) encoding repressor(s) or timer(s). The repressor(s) or timer(s) delay expression of the target molecule(s).
Claims25
A composition comprising:
- (a) a first polynucleotide comprising (i) a repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- and
- (b) a second polynucleotide comprising a sequence encoding a fusion polypeptide comprising (i) a repressor that binds to the repressor binding element, and (ii) a destabilization domain, wherein binding of the repressor to the repressor binding element reduces translation of the first polypeptide from the first polynucleotide, and wherein the destabilization domain enhances degradation of the repressor.
A method of expressing a first polypeptide in a cell, the method comprising contacting the cell with:
- (a) a first polynucleotide comprising (i) a repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- and
- (b) a second polynucleotide comprising a sequence encoding a fusion polypeptide comprising (i) a repressor that binds to the repressor binding element, and (ii) a destabilization domain,
- wherein binding of the repressor to the repressor binding element reduces translation of the first polypeptide from the first polynucleotide, and wherein the destabilization domain enhances degradation of the repressor.
1 more element
A method of expressing a first polypeptide in a subject, the method comprising administering to the subject:
- (a) a first polynucleotide comprising (i) a repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- and
- (b) a second polynucleotide comprising a sequence encoding a fusion polypeptide comprising (i) a repressor that binds to the repressor binding element, and (ii) a destabilization domain,
- wherein binding of the repressor to the repressor binding element reduces translation of the first polypeptide from the first polynucleotide, and wherein the destabilization domain enhances degradation of the repressor.
1 more element
A composition comprising
- (a) a first polynucleotide comprising (i) a repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- (b) a second polynucleotide comprising an open reading frame encoding a second polypeptide;
- and
- (c) a third polynucleotide comprising a sequence encoding a fusion polypeptide comprising (i) a repressor that binds to the repressor binding element, and (ii) a destabilization domain;
- and
- wherein binding of the repressor to the repressor binding element reduces translation of the first polypeptide from the first polynucleotide, and wherein the destabilization domain enhances degradation of the repressor.
3 more elements
A composition comprising
- (a) a first polynucleotide comprising (i) a first repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- (b) a second polynucleotide comprising (i) a second repressor binding element, and (ii) an open reading frame encoding a second polypeptide;
- (c) a third polynucleotide comprising a sequence encoding a first fusion polypeptide comprising (i) a first repressor that binds to the first repressor binding element, and (ii) a first destabilization domain;
- and
- (d) a fourth polynucleotide comprising a sequence encoding a second fusion polypeptide comprising (i) a second repressor that binds to the second repressor binding element, and (ii) a second destabilization domain;
- and
- wherein binding of the first and second repressors to the first and second repressor binding elements respectively reduce translation of the first and second polypeptides from the first and second polynucleotides, and wherein the first and second destabilization domains respectively degrade the first and second repressors at different rates.
4 more elements
A composition comprising
- (a) a first polynucleotide comprising (i) a first repressor binding element, and (ii) an open reading frame encoding a first polypeptide;
- (b) a second polynucleotide comprising (i) a second repressor binding element, and (ii) an open reading frame encoding a second polypeptide;
- (c) a third polynucleotide comprising an open reading frame encoding a third polypeptide;
- (d) a fourth polynucleotide comprising a sequence encoding a first fusion polypeptide comprising (i) a first repressor that binds to the first repressor binding element, and (ii) a first destabilization domain;
- and
- (e) a fifth polynucleotide comprising a sequence encoding a second fusion polypeptide comprising (i) a second repressor that binds to the second repressor binding element, and (ii) a second destabilization domain;
- and
- wherein binding of the first and second repressors to the first and second repressor binding elements respectively reduce translation of the first and second polypeptides from the first and second polynucleotides, and wherein the first and second destabilization domains respectively degrade the first and second repressors at different rates.
5 more elements
Dependencies are inferred from the claim text.