Abstract: The present disclosure is directed to designed fusion proteins derived from MTFs with strong potency to modulate transcription and designated these recombinant fusion proteins MSN and NMS. These powerful transactivators potently activate transcription from endogenous loci when recruited through CRISPR-dCas9, Zinc Finger, or TALE system proteins. This technology permits upregulation of gene expression in targeted manner devoid of viral transcription activation domains and is amenable to high-throughput screening. These synthetic transcription activators interact with all programable DNA binding proteins tested and have exhibited applicability in vitro for efficient lineage conversion.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

Abstract: An engineered cell expressing a therapeutic agent and a reporter agent, the engineered cell comprising a first transgene containing a light sensing DNA sequence encoding a light sensing protein, and a second transgene containing a calcium activated promoter, a therapeutic agent DNA encoding a therapeutic agent, and a reporter agent DNA encoding a reporter agent.

Abstract: The present disclosure provides expression constructs designed to provide for stable and/or inducible, tightly controlled production of genetically encoded payloads from engineered cells. These cassettes allow cells to be engineered to express genetically encoded payloads despite epigenetic silencing. As such, provided herein are expression systems for use in methods to engineer cells using CRISPR dCas9-activator systems such that expression of genetically encoded payloads (e.g., therapeutic proteins) can be optimized to overcome epigenetic silencing. In addition, provided herein are engineered cells comprising the expression systems.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

Abstract: Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.