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.

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.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors containing a synthetic zinc finger transcriptional effector (synZTE) module, engineered to modulate gene expression and cellular activities in a ligand-dependent manner. The new Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit (NEC), which includes the negative regulatory region (NRR) previously believed to be essential for the functioning of Notch receptors, is partly or completely deleted. In addition, the synZTE is designed to bind orthogonal DNA target sequences in target organisms which in turn facilitates precise regulation of therapeutic gene expression with minimal off-target activity. Also provided are compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as cancers.

The present invention provides for a novel peptide and method for treating polyglutamine (polyQ) diseases. Also disclosed are related compositions and kits for therapeutic use in the treatment of polyQ diseases.

Provided are antigen-density sensing molecular circuits and methods of using the same. Aspects of such circuits will generally include an antigen-triggered switch component and a therapeutic component specific for the same antigen as the antigen-triggered switch component. The circuits will generally be configured such that expression of the therapeutic component is induced by the antigen-triggered switch component when the switch is activated by binding the antigen. Nucleic acids, expression constructs, vectors and the like encoding such circuits, and cells genetically modified to include an antigen-density sensing molecular circuit are also provided. Also provided are methods of making antigen-density sensing molecular circuits, methods of inducing expression of high affinity therapeutics specific to an antigen expressed by a target cell, methods of activating an immune response to a target cell, methods of treating a subject for a cancer expressing an antigen, and the like, where such methods involve antigen-density sensing molecular circuits.

The present disclosure generally relates to, inter alia, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. Particularly, the new receptors, even though derived from Notch, do not require the Notch negative regulatory regions previously believed to be essential for the functioning of the receptors. In addition, the new receptors described herein incorporate an extracellular oligomerization domain to promote oligomer formation of the chimeric receptors. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as cancers.

Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the anti-PMCA antigen binding domains disclosed herein. SynNotch receptors that comprise an anti-PSCA binding domain Provided are polynucleotides encoding antibodies, fragments thereof, CARs, T cell receptors (TCR) and SynNotch receptors. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Disclosed herein are polypeptides for use in treating diseases associated with pathogenic genomic repeat sequences, such as neurological disorders. Also disclosed are nucleic acid molecules and vectors that encode such polypeptides. Therapeutic uses and methods for treating such diseases are also disclosed; in particular, therapeutic uses and methods comprising complementary pairs and combinations of therapeutic polypeptides, nucleic acids or vectors. Also disclosed is a method and associated peptides and nucleic acids for active, long-term delivery of therapeutic molecules to target cells in vivo or in vitro.