Provided herein are new compositions and methods to target pharmaceutical agents to pathological areas by utilizing fusion polypeptides. These fusion polypeptides contain two or more domains: (i) aptamer sequences that bind to exposed collagenous (XC-) proteins present in pathological areas, including cancerous and viral lesions, (ii) immunomodulators, such as cytokines, and optionally (iii) at least one linker joining the two domains or at the terminus of the polypeptide. In some cases, the linker is a rigid linker, e.g., a rigid helical linker. Also provided herein are methods of treating cancer and/or infectious diseases using the new fusion polypeptides.

Disclosed herein are methods for inducing immunity against a severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2) in a patient in need thereof. The method comprises administering a vaccine composition comprising a self-adjuvanted SARS-CoV2 Spike (S) RNA-based vaccine (AAHI-SC2), followed by administering a replication defective adenovirus (hAd5) vaccine composition, wherein the adenovirus comprises an E1 gene region deletion and an E2b gene region deletion.

A living engineered biofilm material comprises microbial cells embedded in a protective extracellular matrix comprising a fusion protein of an amyloid domain and a contaminant binding domain operative to bind a contaminant of a water source, and thereby facilitate decontamination of the water source.

The present invention relates to antibody molecules and peptide delivery systems for use in the treatment and management of Alzheimer's disease and related disorders. In particular, the antibody molecules preferentially bind oligomeric forms of beta-amyloid peptide, in single domain format, and the peptide delivery systems facilitate specific transport of such antibody molecules, as well as other cargo molecules, across the blood-brain barrier. The invention also relates to constructs of the antibody molecules and the delivery peptides, as well as pharmaceutical compositions comprising effective amounts of the antibody molecules, delivery peptides, and/or their constructs, including humanized versions of the antibody molecules and constructs. The invention further relates to methods of making these products and pharmaceutical compositions thereof; and methods of using the pharmaceutical compositions in treating or preventing Alzheimer's and related disorders, such as those involving accumulation of beta-amyloid peptide or other peptides that aggregate in the brain; as well as to methods and kits for diagnosing these disorders.

The present disclosure provides a fusion protein useful for treating a non-nuclear organelle associated disorder, such as a genetic disorder, e.g., Friedrich's Ataxia. The fusion protein may comprise a protein of interest to be delivered to a non-nuclear organelle; an organelle targeting sequence (OTS); a cell penetrating peptide (CPP); and a target enhancing sequence (TES); wherein the CPP is capable of interference with delivery of the protein of interest to the non-nuclear organelle; and wherein the TES prevents said interference by the CPP. The fusion protein may also comprise a protein of interest to be delivered to a non-nuclear organelle; a CPP and a TES. The present disclosure also provides methods for treating a non-nuclear organelle associated disorder by administering the fusion protein to a subject in need thereof.

A protein transduction domain and a fusion compound, which are more efficient, are proposed. As a result of selecting and testing a number of candidate peptides, the present inventors found that a GK1 peptide comprising 18 amino acids and a modified sequence obtained by replacing, adding, or deleting some sequences are bonded to high-molecular-weight materials such as proteins based on the basic sequence of the peptide, thus enabling the high-molecular-weight materials to smoothly penetrate into living bodies, for example, cells, tissues, or blood. A fusion compound, oligonucleotide, or vector using the same may be applied as a pharmaceutical composition for preventing or treating diseases.

A method of introducing a foreign substance from the outside of eukaryotic cells into at least a cytoplasm of the cells in vitro or in vivo disclosed here includes the following steps: (1) preparing a construct for introducing a foreign substance, wherein the construct includes a carrier peptide fragment composed of the following amino acid sequence: TLKERCLQVVRSLVKKKRTLRKNDRKKR (SEQ ID NO: 1), and the foreign substance bound to an N-terminal side and/or C-terminal side of the carrier peptide fragment; (2) supplying the construct into a sample containing target eukaryotic cells; and (3) incubating the sample to which the construct is supplied, wherein the construct is introduced into the target eukaryotic cells in the sample.

RNA replicons encoding stabilized recombinant pre-fusion SARS CoV-2 S proteins are described. Also described are pharmaceutical compositions and uses of the RNA replicons.

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Fusion proteins for immunotherapy against cancer and infectious diseases are disclosed. A fusion protein according to the invention comprises a CD40-binding domain; an antigen; and a translocation domain located between the CD40-binding domain and the antigen, in which a furin and/or cathepsin L cleavage site is present in the fusion protein between the CD40-binding domain and the translocation domain. The antigen is an antigen of a pathogen or a tumor antigen. The furin and/or cathepsin L cleavage site permits removal of the CD40-binding domain away from the fusion protein via furin and/or cathepsin L cleavage. Also disclosed are pharmaceutical compositions, expression vectors and use of the fusion proteins of the invention for eliciting an antigen-specific cell-mediated immune response, treating a tumor and/or a disease caused by a pathogen in a subject in need thereof.