Boston University

The General Hospital Corporation

Ahmad S Khalil

Minhee Park

Divya Israni

J Keith Joung

James Joseph Collins

Jeffry D Sander

Wilson Wai Chun Wong

Huishan Li

Nikit Patel

Albert J Keung

Caleb J Bashor

Embodiments disclosed herein provide artificial expression systems comprising multivalent transcription factor complexes for cooperative transcription factor assembly and modulating gene expression. More specifically, engineered synthetic transcription factors are recruited and structurally organized on synthetic gene circuits using molecular clamps, where the strength of intra-complex interactions can be modulated for fine tuning of gene expression as desired.

Systems and methods for control of gene expression

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 effector domain, and 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.

Regulated synthetic gene expression systems

Provided herein are engineered systems and methods for establishing DNA adenine methylation at specific genomic locations and using DNA adenine methylation as an artificial chemical 'handle' on the genome. These systems and methods allow for placing the handle on specific genomic locations as well as molecular technologies to bind, spatially spread, and maintain the handle. The systems described herein comprise, in some embodiments, three functional modules that mediate m6A operations: (1) a synthetic initiator module to place m6A at specific genomic sites; (2) a synthetic readout module to program m6A recognition and m6A-dependent transcriptional logic; and (3) propagation module that implements 'read-write,' a mechanism proposed to underlie chromatin spreading and epigenetic maintenance across cellular systems.

Integrated system for programmable DNA methylation

Embodiments disclosed herein provide artificial expression systems comprising the zinc-finger containing transcription factors and engineered promoters to modulate expression of genes of interest. Engineered zinc-finger transcription factors that interact with engineered promoters constitute synthetic and regulatable expression systems which facilitate the modulation of gene expression as desired.

Synthetic transcriptional and epigenetic regulators based on engineered, orthogonal zinc finger proteins

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Lexington, MA, United States of America

Ahmad S Khalil