The disclosure describes methods that include providing a first nucleic acid having a sequence encoding a first set comprising one or more transcription activator-like effector (TALE) repeat domains and/or one or more portions of one or more TALE repeat domains; contacting the first nucleic acid with a first enzyme, wherein the first enzyme creates a first ligatable end; providing a second nucleic acid having a sequence encoding a second set comprising one or more TALE repeat domains and/or one or more portions of one or more TALE repeat domains; contacting the second nucleic acid with a second enzyme, wherein the second enzyme creates a second ligatable end, and wherein the first and second ligatable ends are compatible; and ligating the first and second nucleic acids through the first and second ligatable ends to produce a first ligated nucleic acid, wherein the first ligated nucleic acid is linked to a solid support, and wherein the first ligated nucleic acid encodes a polypeptide comprising said first and second sets.

Provided herein are modified forms of Conantokin peptides, including, modified Con-P peptides, nucleic acids encoding the same and compositions thereof. Further provided are nucleic acid molecules encoding for chimeric modified conantokin polypeptides to be expressed in or on a membrane of a target cells, compositions comprising the same and uses thereof for treating various neurodegenerative conditions.

Provided herein are compositions, systems, kits, and methods for expressing a peptide of interest, such as Apolipoprotein H (ApoH), also known as β2-glycoprotein I (β2GPI), at increased levels using a non-ApoH signal peptide (e.g., a signal peptide that permits increased protein export from cells). Also provided herein are compositions, systems, kits, and methods for employing such recombinant ApoH with a non-ApoH signal peptide to detect subject Apolipoprotein H antibodies in a sample from a subject (e.g., to diagnose antiphospholipid syndrome in a subject).

Provided herein is a family of programmable de novo designed transmembranal protein domain polypeptides, and uses thereof in the production of engineered chimeric antigen receptor T (CAR T) cells, which are used, for example, to fight cancer.

Disclosed are antigen binding polypeptides and antigen binding polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural features. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells, chimeric antigen receptors (CARs), immune cells, pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

Provided are isolated nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind to tumor antigens. Also provided are isolated polypeptides and CARs encoded by the isolated nucleic acid molecules, vectors that include the isolated nucleic acid molecules, cells that include the isolated nucleic acid molecules, methods of making the same, and methods for using the same to generate a persisting population of genetically engineered T cells in a subject, expanding a population of genetically engineered T cells in a subject, modulating the amount of cytokine secreted by a T cell, reducing the amount of activation-induced calcium influx into a T cell, providing an anti-tumor immunity to a subject, treating a mammal having a MUC1-associated disease or disorder, stimulating a T cell-mediated immune response to a target cell population or tissue in a subject, and imaging a MUC1-associated tumor.

In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.

The present invention relates to a targeting module comprising at least one PD-L1 and/or PD-L2 binding domain, and a tag-binding domain or a tag for use in a method for stimulating a chimeric antigen receptor mediated immune response in a mammal, a nucleic acid, a vector or a cell comprising a nucleotide sequence encoding the targeting module, a pharmaceutical composition and a kit comprising the targeting module and a vector or a cell comprising a nucleotide sequence encoding a switchable chimeric antigen receptor.

The invention pertains to a method to identify an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein, wherein the combination is effective when the transmembrane E3 ubiquitin ligase is capable of decreasing the surface level of the membrane-bound protein upon forced dimerization, preferably by ubiquitination of the membrane-bound protein. The method of the invention comprises a step of exposing a cell to a heterobifunctional molecule, wherein the heterobifunctional molecule comprises a first binding domain capable of specific binding to an extracellular portion of the transmembrane E3 ubiquitin ligase, and a second binding domain capable of specific binding to an extracellular portion of the membrane-bound protein. The method further comprises a step of determining the decrease in surface level of the membrane-bound protein. The invention additionally pertains to a heterobifunctional molecule targeting an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein.