The present disclosure provides CRISPR-based compositions and methods of their use to impair or promote angiogenesis in a patient to treat indications including, but not limited to, tumor growth, age-related macular degeneration, and metastasis.

The technology described herein is directed to polypeptide systems using drug-controlled peptide docking domains and cognate docking domain-binding peptides and their use to control cellular signaling, activity, and/or gene expression.

Disclosed herein are methods and compositions for modulating expression of a PD1 gene.

Targeted transcriptional effectors (transcription activators and transcription repressors) derived from meganucleases are described. Also described are nucleic acids encoding same, and methods of using same to regulate gene expression. The targeted transcriptional effectors can comprise (i) a meganuclease DNA-binding domain lacking endonuclease cleavage activity that binds to a target recognition site; and (ii) a transcription effector domain.

The present invention provides a transcription activator consisting of not more than 200 amino acid sequences and containing VP64 and a transcription activation site of RTA. The present invention also provides a complex of a nucleic acid sequence-recognizing module specifically binding to a target nucleotide sequence in a double-stranded DNA and the transcription activator.

Compositions, methods, strategies, kits, and systems for the delivery of negatively charged proteins, protein complexes, and fusion proteins, using cationic polymers or lipids are provided. Delivery of proteins into cells can be effected in vivo, ex vivo, or in vitro. Proteins that can be delivered using the compositions, methods, strategies, kits, and systems provided herein include, without limitation, enzymes, transcription factors, genome editing proteins, Cas9 proteins, TALEs, TALENs, nucleases, binding proteins (e.g., ligands, receptors, antibodies, antibody fragments; nucleic acid binding proteins, etc.), structural proteins, and therapeutic proteins (e.g., tumor suppressor proteins, therapeutic enzymes, growth factors, growth factor receptors, transcription factors, proteases, etc.), as well as variants and fusions of such proteins.

The present invention concerns the use of a protein comprising at least a HIV-derived accessory protein tat (trans-activator of transcription) or any derivative thereof for the reactivation of latent human immunodeficiency virus (HIV) from cells present in a HIV-infected patient.

Described herein are polypeptides, systems, and methods that relate to using domains that bind specifically to a biotinylamide to control receptor and cellular activity.

Provided herein is a recombinant or engineered Cas9 protein. The Cas9 protein has an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2. The Cas9 protein has at least one mutation in an amino acid residue selected from 262, 324, 409, 480, 543, 694, of the amino acid sequence provided in SEQ ID NO: 2 or the corresponding residue of an aligned sequence, and at least one mutation in an amino acid residue selected from 1111, 1135, 1218, 1219, 1322, 1335, and 1337, of the amino acid sequence provided in SEQ ID NO: 2 or the corresponding residue of an aligned sequence. The amino acid sequence of the recombinant Cas9 protein is not identical to the amino acid sequence of a naturally occurring Cas9 protein.

In one aspect, the invention provides a method of screening a human subject to determine if said subject has a genetic predisposition to develop, or is suffering from Facioscapulohumeral Dystrophy (FSHD), said method comprising: (a) providing a biological sample comprising genomic DNA from the subject; and (b) analyzing the portion of the genomic DNA in the sample corresponding to the distal D4Z4-pLAM region on chromosome 4 and determining the presence or absence of a polymorphism resulting in a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene.