Disclosed herein are compositions comprising one or more therapeutic proteins for oral administration. The disclosed proteins, which may be directed to a variety of GI and systemic target antigens, resist denaturation and degradation in the stomach and intestines of a patient. The disclosed proteins may be delivered intact to a target region within the gut, or anywhere in body to target specific molecules, cells, tissues, or organs. In some embodiments, the disclosed proteins may include two or more proteins for targeting two or more target antigens.

Multivalent D-peptidic compounds that specifically bind to a target protein are provided. The multivalent D-peptidic compounds can include two or more distinct variant D-peptidic domains connected via linking components. The D-peptidic compounds can include multiple distinct domains that specifically bind to different binding sites on a target protein to provide for high affinity binding to, and potent activity against, the target protein. D-peptidic variant GA and Z domain polypeptides are also provided, which polypeptides have specificity-determining motifs (SDM) for specific binding to a target protein, such as VEGF-A or PD-1. In some embodiments where the target protein is homodimeric (e.g., VEGF-A, PD-1), the D-peptidic compounds may be similarly dimeric, and include a dimer of multivalent (e.g., bivalent) D-peptidic compounds. Methods for using the compounds are provided, including methods for treating a disease or condition associated with a target protein in a subject.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

Provided are compositions comprising an activatable proprotein comprising a first IL-15 or a variant thereof and a second IL-15Rα or variant thereof fused to a masking moiety comprising an antibody Fc region, and methods of using the same for cancer immunotherapy and other therapies.

Described herein are compositions, kits and methods for shredding the genomes of selected cell types, for example, the genomes of selected cancer cell types.

Compositions for CDKL5 gene therapy are provided, as well as recombinant CDKL5 proteins. Such CDKL5 gene therapy compositions and/or recombinant CDKL5 proteins may incorporate cell-penetrating polypeptides and/or leader signal polypeptides. Also provided are methods of producing such gene therapy compositions and recombinant CDKL5 proteins, as well as pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and recombinant CDKL5 proteins.

The present disclosure relates to a multi-functional nanoparticle targeted to breast cancer, a preparation method and use thereof. The multi-functional nanoparticle includes a targeting carrier and a medicament loaded on the targeting carrier; and the targeting carrier is made from recombinant ferritin. Cell experiments verify that the multi-functional nanoparticle has better efficacy and drug release capacity for cancer cells than those of conventional ferritin as a vector. Moreover, the drug delivery system can further achieve optical imaging of tumor cells by loading quantum dots, thus playing a role in cancer diagnosis and treatment.

The present disclosure relates to engineered T cells and methods of making and using the same, as well as reagents for making the engineered T cells.

The present disclosure provides engineered Class 1 Type I CRISPR-Cas (Cascade) systems that comprise multi-protein effector complexes, nucleoprotein complexes comprising Type I CRISPR-Cas subunit proteins and nucleic acid guides, polynucleotides encoding Type I CRISPR-Cas subunit proteins, and guide polynucleotides. Also, disclosed are methods for making and using the engineered Class 1 Type I CRISPR-Cas systems of the present invention.

The present disclosure provides isolated polynucleotides encoding a mature Mycobacterium tuberculosis protein selected from Ag85A, Ag85B, and Ag85C, where the protein does not include a signal for glycosylation, such as a N-glycosylation consensus sequon. Also disclosed are M. tuberculosis proteins selected from Ag85A, Ag85B, and Ag85C that do not include a signal for glycosylation, such as a N-glycosylation consensus sequon, and/or are not glycosylated, and methods for using the polynucleotides and proteins.