Synthetic circuits and uses thereof
AssigneeStrand Therapeutics Inc.
InventorsTasuku KITADA, Jaspreet KHURANA, Wen Allen TSENG, Justin LETENDRE, Rachel EICHMAN, Sarah BENING, Aidan SIMPSON, Dahyana ARIAS ESCAYOLA
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Abstract
The present disclosure relates to a synthetic circuit that can be used to selectively express a payload in a target cell. In some aspects, a synthetic circuit comprises a payload sequence comprising a sensor and a regulator sequence comprising a sensor. Also provided herein are methods of using such synthetic circuits to treat a wide range of disease or disorders.
Claims163
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence),
- wherein the payload sequence comprises a sensor that is capable of specifically recognizing the regulator (type P sensor),
- wherein the regulator sequence comprises a sensor that is capable of specifically recognizing a marker (type R sensor), and
- wherein the regulator and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence),
- wherein the payload sequence comprises a first sensor that is capable of specifically recognizing the regulator (first type P sensor) and a second sensor that is capable of specifically recognizing a marker (second type P sensor),
- wherein the regulator sequence comprises a sensor that is capable of specifically recognizing a marker (type R sensor), and
- wherein the regulator, the marker recognized by the second type P sensor (second type P marker), and/or the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a self-replicating RNA and comprises a sensor that is capable of specifically recognizing the regulator (type P sensor);
- wherein the regulator sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a self-replicating RNA and comprises a first sensor that is capable of specifically recognizing the regulator (first type P sensor) and a second sensor that is capable of specifically recognizing a marker (second type P sensor);
- wherein the regulator sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator, the marker recognized by the second type P sensor (type P marker), and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a self-replicating RNA comprises a sensor that is capable of specifically recognizing the regulator (type P sensor);
- wherein the regulator sequence is a non-replicating linear RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a self-replicating RNA and comprises a first sensor that is capable of specifically recognizing the regulator (first type P sensor) and a second sensor that is capable of specifically recognizing a marker (second type P sensor);
- wherein the regulator sequence is a non-replicating linear RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator, the marker recognized by the second type P sensor (type P marker), and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing the regulator (type P sensor);
- wherein the regulator sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a circular RNA and comprises a first sensor that is capable of specifically recognizing the regulator (first type P sensor) and a second sensor that is capable of specifically recognizing a marker (second type P sensor);
- wherein the regulator sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator, the marker recognized by the second type P sensor (type P marker), and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a circular RNA and comprises a sensor that is capable of specifically recognizing the regulator (type P sensor);
- wherein the regulator sequence is a non-replicating linear RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and (b) a second nucleotide sequence encoding a regulator (regulator sequence);
- wherein the payload sequence is a circular RNA and comprises a first sensor that is capable of specifically recognizing the regulator (first type P sensor) and a second sensor that is capable of specifically recognizing a marker (second type P sensor);
- wherein the regulator sequence is a non-replicating linear RNA and comprises a sensor that is capable of specifically recognizing a marker (type R sensor);
- and
- wherein the regulator, the marker recognized by the second type P sensor (type P marker), and the marker recognized by the type R sensor (type R marker) are not the same.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence),
- wherein, when the payload sequence and the regulator sequence are present in a target cell, the payload is expressed in the target cell for a first expression and the regulator is expressed in the target cell for a second expression, and
- wherein the first expression is greater than the second expression.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence),
- wherein, when the payload sequence and the regulator sequence are present in a non-target cell, the payload is expressed in the non-target cell for a first expression and the regulator is expressed in the non-target cell for a second expression, and
- wherein the second expression is greater than the first expression.
A synthetic circuit comprising:
- (a) a first nucleotide sequence encoding a payload (payload sequence) and
- (b) a second nucleotide sequence encoding a regulator (regulator sequence),
- wherein, when the synthetic circuit is contacted with a population of cells comprising a target cell and a non-target cell, the expression of the payload in the target cell is higher than the corresponding expression in the non-target cell.
Dependencies are inferred from the claim text.