Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1(NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Disclosed are adeno-associated virus (AAV) vectors comprising a nucleotide sequence encoding RP2 or RPGR-ORF15 and related pharmaceutical compositions. Also disclosed are methods of treating or preventing X-linked retinitis pigmentosa, increasing photoreceptor number in a retina of a mammal, and increasing visual acuity of a mammal using the vectors and pharmaceutical compositions.

A protein-based probe for detecting the presence of one of two distinct states of a target membrane-associated molecule by means of polarization microscopy is disclosed. The probe contains an anchoring moiety consisting of at least one lipidated peptide and/or at least one transmembrane α-helical peptide, a peptide linker moiety having the length of at least 5 amino acids, wherein at least 50% of the amino acids forming the linker are selected from glycine, serine, and threonine, a fluorescent moiety, and an affinity binding moiety capable of binding the target membrane-associated molecule. The moieties are arranged in the order a-b-c-d or d-c-b-a in the direction from the N-terminus to the C-terminus. Methods of detecting presence or absence of the target molecule, detecting activated or inactive forms of the target molecule, and detecting the activation of the target molecule are also described.

The present disclosure relates generally to compositions and methods suitable for treating a disorder associated with loss-of-function mutations in SYNGAP1. More specifically, the disclosure relates to methods for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1, and to antisense oligonucleotides specific for SYNGAP1 and their use for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1.

Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.

Disclosed are adeno-associated virus (AAV) vectors comprising a nucleotide sequence encoding RP2 or RPGR-ORF15 and related pharmaceutical compositions. Also disclosed are methods of treating or preventing X-linked retinitis pigmentosa, increasing photoreceptor number in a retina of a mammal, and increasing visual acuity of a mammal using the vectors and pharmaceutical compositions.

Disclosed are adeno-associated virus (AAV) vectors comprising a nucleotide sequence encoding RP2 or RPGR-ORF15 and related pharmaceutical compositions. Also disclosed are methods of treating or preventing X-linked retinitis pigmentosa, increasing photoreceptor number in a retina of a mammal, and increasing visual acuity of a mammal using the vectors and pharmaceutical compositions.

The present invention relates to G protein peptidomimetics capable of stabilizing a GPCR in an active conformational state. The G protein peptidomimetics are derived from the G protein epitope interacting with the GPCR, in particular from the C-terminus of the as helix comprising the amino acid sequence FNDCRDIIQRMHLRQYELL (SEQ ID NO:117). The invention further provides complexes of the G protein peptidomimetics and a GPCR, fusion polypeptides of a GPCR and the G protein peptidomimetics and compositions comprising the same. Further disclosed herein are uses of the G protein peptidomimetics, complexes, fusion polypeptides and compositions for determining the structure of the GPCR conformer and for screening for compounds capable of specifically binding to the GPCR conformer.

The disclosure provides gene therapy compositions and methods for treating tuberous sclerosis. In particular, the disclosure provides compositions comprising recombinant adeno-associated viruses (rAAVs) comprising an AAV capsid protein, and an AAV expression cassette encoding condensed Tuberins (cTuberins), and methods of use thereof.