Provided herein are compositions and methods for modifying a predetermined nucleic acid sequence. A programmable nucleoprotein molecular complex containing a polypeptide moiety and a specificity conferring nucleic acid (SCNA) which assembles in-vivo, in a target cell, and is capable of interacting with the predetermined target nucleic acid sequence is provided. The programmable nucleoprotein molecular complex is capable of specifically modifying and/or editing a target site within the target nucleic acid sequence and/or modifying the function of the target nucleic acid sequence.

It is an object of the present invention to provide, for instance, a method for evaluating a function, such as transforming potential, of multiple different genes of interest, and a method capable of evaluating drug sensitivity of a subject having each gene of interest. The present invention relates to, for instance, a method for evaluating multiple different genes of interest, comprising the steps of: integrating, into host cell genomic DNA, polynucleotides each comprising a tag sequence and a gene of interest or a fragment thereof linked to the tag sequence; mixing a plurality of different host cells having the different polynucleotides integrated therein; culturing the mixed host cells; extracting the genomic DNA from the cultured host cells; quantifying each of the polynucleotides in the extracted genomic DNA based on the tag sequence; and determining a relative cell count of each of the host cells having the respective polynucleotides after the culturing, based on the quantified values for the polynucleotides.

The present invention provides a method for producing a fermentation product by culturing recombinant exosporium-producing Bacillus cells that express a fusion protein of interest on the exosporium in a medium containing sources of carbon and nitrogen in a total concentration of at least 20 g/L, resulting in a fermentation broth containing a high titer of the recombinant Bacillus spores.

Provided herein are modified immunoglobulins comprising an amyloid reactive peptide joined to an antibody, as well as humanized antibodies that bind to human amyloid fibrils and antibody-peptide fusion proteins. Also provided herein are methods of treating amyloid-based diseases by administering a modified immunoglobulin, humanized antibody, or antibody-peptide fusion protein.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Angelman Syndrome (AS) is a genetic disorder occurring in approximately one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.

The present application relates to a compositions and methods comprising or expressing a hevamine A-related MoMo30 protein from Momordica balsamina. The MoMo30 protein is about 30 kDa in size, is stable after being autoclaved at 120° C. for 30 min, resists proteolytic cleavage by trypsin, exhibits mannose-sensitive binding to HIV gp120, exhibits hemagglutinin and chitinase activity, is capable of activating and stimulating T cell proliferation, is capable of preventing infection by HIV-1 or alleviating symptoms in an HIV-1 infected patients, and comprises an amino acid sequence of SEQ ID NO: 4. The MoMo30 protein and/or a nucleic acid encoding the same may be used in methods for preventing or treating microbial infections by HIV, SARS-CoV-2 and other enveloped viruses, as well as other microorganisms comprising cell surface proteins containing glycan residues, such as mannose.

The present invention relates to compositions of recombinant polynucleic acid constructs comprising at least one nucleic acid sequence encoding an siRNA capable of binding to a target mRNA and at least one nucleic acid sequence encoding a gene of interest. Also disclosed herein is use of the compositions in treating a disease or a condition and in simultaneously modulating expression of two or more genes.

Provided herein are extracellular vesicle (EV) (a.k.a. exosome) compositions for specifically targeting the delivery of a therapeutic agent to particular cells and/or tissues in a subject, as well as methods of making and methods of using said compositions. The compositions and methods disclosed herein are useful for targeted drug delivery in the treatment of diseases in which a cell surface receptor is overexpressed, such as, for example, cancer.