Activity-dependent expression of nucleic acids
AssigneeCalifornia Institute of Technology
InventorsDavid J. Anderson, Todd E. Anthony
Life of this patent
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Abstract
According to some embodiments herein, expression systems and methods for activity-dependent transcription of nucleic acids are provided. In some embodiments, adeno-associated viral vector systems comprise an immediate early gene promoter operably linked to a transcriptional activator. The transcription activator can be fused to an N-terminal portion of an immediate early gene, for example fos.
Claims26
An activity-dependent adeno-associated virus (AAV) vector expression system comprising:
- an immediate early gene (IEG) promoter operably linked to a converter nucleic acid encoding a converter comprising an N-terminal portion of FOS fused to a nucleic acid encoding an activator, wherein the activator is downstream of the N terminal portion of FOS;
- and
- a regulatable promoter operably linked to an insertion site for a transcript-encoding nucleic acid, wherein transcription by the regulatable promoter is activated by the activator, and
- wherein the activator's activation of the regulatable promoter is modulated by a transcriptional modulator compound, if present.
A method of activity-dependent expression of a nucleic acid in an animal cell, the method comprising:
- contacting an adeno-associated virus (AAV) vector system in the animal cell with a transcriptional modulator compound, said AAV vector system comprising:
- an immediate early gene (IEG) promoter operably linked to a converter nucleic acid encoding an N-terminal portion of FOS fused to an activator, wherein the activator is downstream of the N terminal portion of FOS;
- a regulatable promoter operably linked to a transcript-encoding nucleic acid, wherein the activator activates transcription by the regulatable promoter, and wherein the activator's activation of transcription is inhibited by the transcriptional modulator compound;
- and
- an other promoter operably linked to a silencer nucleic acid encoding a silencer;
- wherein the silencer represses transcription by the regulatable promoter, and wherein the silencer's repression of transcription is induced by the transcriptional modulator compound;
- and
- ceasing said contacting by said transcriptional modulator compound, whereby the activator is no longer inhibited, thereby expressing the nucleic acid from the IEG promoter when the animal cell is activated.
A method of activity-dependent nucleic acid expression in an animal cell, the method comprising:
- contacting an adeno-associated virus (AAV) vector system in the animal cell with a transcriptional modulator compound, said AAV vector system comprising:
- an immediate early gene (IEG) promoter operably linked to a converter nucleic acid encoding an N-terminal portion of FOS fused to an activator, wherein the activator is downstream of the N terminal portion of FOS;
- a regulatable promoter operably linked to a transcript-encoding nucleic acid, wherein the activator activates transcription by the regulatable promoter, and wherein the activator's activation of transcription is activated by the transcriptional modulator compound,
- thereby expressing the transcript-encoding nucleic acid from the IEG promoter when the animal cell is activated.
Dependencies are inferred from the claim text.