The present invention provides methods for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.

Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldanstrom macroglobulinemia.

Described herein are transcriptional relay systems useful for reducing background signal in protein expression and reporter assays. These systems utilize a nucleic acid system wherein a promoter sequence controls expression of a synthetic transcription factor that activates transcription of a reporter molecule.

The present disclosure relates to a mammalian cell line for producing adeno-associated virus (AAV), suitably including nucleic acids encoding helper genes and AAV genes, under the control of derepressible promoters. The disclosure also relates to isolated nucleic acid molecules that encode such genes, as well as methods of using the mammalian cells for producing AAVs.

The present disclosure provides an automated method of producing viral vectors, utilizing engineered viral vector-producing cell lines within a fully-enclosed cell engineering system. Exemplary viral vectors that can be produced include lentivirus vectors, adeno-associated virus vectors, baculovirus vectors and retrovirus vectors.

The present invention provides methods and compositions for labeling and/or targeting cells with increased calcium by providing a CREB reporter system. In addition, methods of treating disorders with activated cells such as brain disorders or cancer are also provided herein.

Provided herein are sequestrons for detecting an miRNA profile indicative of a cell state and expressing an output molecule in cells having such an miRNA profile. Also provided are methods of using sequestrons provided herein.

The present disclosure provides polypeptides, compositions thereof, and methods for suppressing expression of a target gene such as PDCD1, CTLA4, LAG3, or TIM-3. The polypeptides disclosed herein include a DNA binding domain (DBD) that binds to a sequence of the target gene and a transcriptional repressor domain that suppresses expression of the target gene. The transcriptional repressor domain may be a known transcriptional repressor or may be a novel transcriptional repressor disclosed herein. Also disclosed herein are novel transcriptional repressors that are conjugated to a heterologous DNA binding domain and mediate suppression of expression of a target gene bound by the DNA binding domain.

This disclosure describes a programmable transcription factor system. Generally, the system includes a programmable transcription factor, a polynucleotide that includes a coding region whose expression is either required or toxic for cell viability, and a promoter operably linked to the polynucleotide and having a binding site for the programmable transcription factor. The programmable transcription factor generally includes a domain that specifically binds to a promoter and a domain that either activates transcription (if the polynucleotide encodes an essential product) or represses transcription (if the polynucleotide encodes a toxic product).

The present invention relates to expression system for establishing a transgenic differentiation-control network useful for controlling cell differentiation.