Cas9-based transcription modulation systems
AssigneePresident and Fellows of Harvard College
InventorsAlejandro Chavez, Nan Cher Yeo
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Abstract
The present disclosure provides methods and compositions of modulating expression of a target nucleic acid in a eukaryotic cell. The methods include providing to the cell a guide RNA complementary to the target nucleic acid sequence, providing to the cell a fusion protein, wherein the fusion protein comprises a nuclease null Cas9 protein and a transcriptional effector domain, wherein the nuclease null Cas9 protein interacts with the guide RNA and binds to the target nucleic acid sequence in a site specific manner and wherein the transcriptional effector domain modulates expression of the target nucleic acid.
Claims9
A method of modulating expression of a target nucleic acid in a eukaryotic cell comprising providing to the cell a guide RNA complementary to the target nucleic acid sequence, providing to the cell a fusion protein, wherein the fusion protein comprises a nuclease null Cas9 protein (dCas9) and an effector domain, wherein the effector domain comprises a fusion of two or more transcriptional repressor domains selected from the group consisting of Kruppel-associated box (KRAB), MeCP2, SIN3A, HDT1, MBD2B, NIPP1, and HP1A, and wherein the nuclease null Cas9 protein interacts with the guide RNA and binds to the target nucleic acid sequence in a site specific manner and wherein the effector domain modulates expression of the target nucleic acid.
Dependencies are inferred from the claim text.