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.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

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.

Some aspects of this disclosure provide a fusion protein comprising a guide nucleotide sequence-programmable DNA binding protein domain (e.g., a nuclease-inactive variant of Cas9 such as dCas9), an optional linker, and a recombinase catalytic domain (e.g., a tyrosine recombinase catalytic domain or a serine recombinase catalytic domain such as a Gin recombinase catalytic domain). This fusion protein can recombine DNA sites containing a minimal recombinase core site flanked by guide RNA-specified sequences. The instant disclosure represents a step toward programmable, scarless genome editing in unmodified cells that is independent of endogenous cellular machinery or cell state.

The current disclosure relates to methods and compositions for increasing functional expression of BRD9 in a cell. The methods and compositions can be incorporated into methods for treating cancer through the administration of BRD9 activating therapies. Accordingly, aspects of the disclosure relate to compositions and methods for treating cancer, a pre-malignant disease, or a dysplastic disease in a subject. The method can comprise administering a BRD9 activating therapy to the subject.

The present disclosure relates to CRISPR-Cas systems that utilize Cas 12J for editing nucleic acids in plants. Methods and compositions for using these systems for editing nucleic acids in plants are provided herein.

Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

The present application relates to ligands targeted to epidermal growth factor receptor (EGFR) and compositions for use in treating tumors. Specifically, a ligand targeted to EGFR is disclosed. The ligand comprises a heavy chain variable domain and a light chain variable domain. The ligand may be selected from the group consisting of a single chain variable fragment, a fusion protein, a monoclonal antibody, and an antigen-binding fragment thereof. The ligand may be conjugated to a liposome or a nanoparticle that encapsulates at least one chemotherapeutic agent to form a ligand-targeted liposomal or nanoparticle drug. Also disclosed are conjugates and formulations for use in treating tumors such as squamous cell carcinoma of head and neck. A method for making a ligand-targeted liposomal drug is also disclosed. The drug may be a chemotherapeutic agent selected from the group consisting of doxorubicine and vinorelbine.

In order to provide a membrane protein production method which does not require the step of solubilizing a membrane protein and which allows the membrane protein having an excellent quality to be obtained with a high yield, a method in accordance with an embodiment of the present invention includes: a step (a) of preparing a reaction solution for cell-free protein synthesis, the reaction solution containing (i) a template nucleic acid which encodes the membrane protein, (ii) a lipid, and (iii) a detergent which is contained at a concentration equal to or higher than a critical micelle concentration; and a step (b) of synthesizing the membrane protein while the concentration of the detergent in the reaction solution is maintained at a concentration equal to or higher than a critical micelle concentration.