Regulated synthetic gene activation systems
AssigneeTrustees of Boston University
InventorsAhmad S. Khalil, Kok Ann Gan, Hanrong Ye, Thea Samuelle Ornstein
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Abstract
The technology described herein is directed to regulated synthetic gene expression systems. In one aspect described herein are synthetic transcription factors (synTFs) comprising a DNA binding domain, a transcriptional activator domain, a transcriptional effector domain (TED), and optionally a regulator protein. In other aspects described herein are gene expression systems comprising said synTFs and methods of treating diseases and disorders using said synTFs.
Claims28
A synthetic transcription factor (synTF) comprising:
- (a) at least one DNA binding domain (DBD),
- (b) a transcriptional activator domain (TA),
- (c) a transcriptional effector domain (TED), which comprises an elongation domain derived from Interacts with Suppressor Of Ty 6 (Spt6) Homolog (IWS1), and
- (d) at least one regulator protein (RP);
- and
- wherein the TED increases the transcriptional activation of the synTF compared to an otherwise identical synTF lacking the TED,
- wherein the TA is directly or indirectly coupled to the DBD, and
- wherein the coupling is regulated by the at least one RP, or
- wherein cellular localization of the TA is regulated by the at least one RP.
A synthetic transcription factor (synTF) comprising:
- (a) at least one DNA binding domain (DBD),
- (b) a transcriptional activator domain (TA), and
- (c) a transcriptional effector domain (TED), which comprises an elongation domain derived from Interacts with Suppressor Of Ty 6 (Spt6) Homolog (IWS1),
- wherein the TED increases the transcriptional activation of the synTF compared to an otherwise identical synTF lacking the TED.
A humanized hybrid transcription activator domain (hhTAD), comprising:
- (a) a transcriptional activator domain (TA), and
- (b) a transcriptional effector domain (TED), which comprises an elongation domain derived from Interacts with Suppressor Of Ty 6 (Spt6) Homolog (IWS1),
- wherein the TED increases the transcriptional activation of the TA compared to an otherwise identical hhTAD lacking the TED;
- and
- wherein the TA and TED are human domains or humanized domains.
Dependencies are inferred from the claim text.