Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

Disclosed herein are methods for generating universal MHC/HLA-compatible hematopoietic progenitor cells and methods for generating custom patient-specific MHC/HLA-compatible hematopoietic progenitor cells. Compositions comprising the universal and custom hematopoietic progenitor cells and therapeutic applications thereof are also disclosed.

The present invention relates to cells and methods for detecting compounds that affect G protein coupled receptor mediated conditions. The invention also relates to methods for treating adverse drug reactions, autoimmune disorders, and pruritus.

The present disclosure relates to a method for generating variants of a protein based on a native protein regulated by allosteric pathway, the method comprising: i) providing 3D structures of the native protein; ii) identifying at least one pair of coupled allosteric sites within the amino acid sequence of the native protein named microswitch; iii) generating in silico mutations of said identified microswitch to generate a pool of variants; iv) computing at least one score reflecting the variation in allosteric coupling; and/or the variation in the relative stability v) predicting the activity of each variant compared to the native protein based on the computed score. The disclosure also concern a computer implemented program to carry out said method, and a variant of a protein or an active fragment thereof, a polynucleotide.

The present invention relates to isolated or purified or partially purified peptide derived molecules having the following general formula (S1): X-[(Pro).sub.n-His-Pro-His-Ala-Arg-Ile-Lys].sub.m-Y. The peptides are for medical use, in particular as anti-tumoral agents.

A method of treating a disorder in a subject. The method comprises administering to said subject an effective amount of an agonist of the melanocortin-4 receptor (MC4R). The subject is a heterozygous carrier of an MC4R mutation, and the disorder results from an attenuated response of MC4R to α-melanocortin stimulating hormone (α-MSH).

Fc-fusion protein derivatives against HIV have enhanced yield in mammalian cells, and extended antiviral and immunomodulatory activities. The Fc-fusion protein derivatives can block the entry of human immunodeficiency virus (HIV) into host cells, elicit effector functions through the activation of natural killer (NK) and other immune system cells, can be produced with high yield in mammalian cells, and have extended activity in vivo. Nucleic acids, vectors and host cells can express the Fc-fusion protein derivatives, which have therapeutic and diagnostic applications in human health.

A novel long-acting acylated oxyntomodulin peptide analogue having dual agonism on GLP-1 and glucagon receptors (dual GLP-1R/GlucagonR agonism) and a pharmaceutical composition including the same are disclosed. The novel long-acting acylated oxyntomodulin peptide analogue and the composition are useful for the prevention and treatment of obesity and overweight, or non-insulin-dependent diabetes accompanied by obesity and overweight. The acylated oxyntomodulin peptide analog has dual agonism for GLP-1/glucagon receptors and has an excellent increased in vivo half-life, and the pharmaceutical composition containing the same is useful for the treatment of metabolic diseases such as obesity and diabetes.

As described below, the present invention features compositions and methods for treating brain and/or behavioral health disorders and their associated symptoms.

The present disclosure relates to methods of determining a treatment course of action. In particular, the present disclosure relates to mutations in the gene encoding estrogen receptor and their association with responsiveness to estrogen therapies for cancer.