An immunogen useful for treating malaria generally includes an immunogenic carrier and an antigenic malaria circumsporozoite protein (CSP) peptide that includes the peptide NPDPNANPNVDPNAN (amino acids 5-19 of SEQ ID NO:1) linked to the immunogenic carrier. The immunogen may be administered to a subject having or at risk of having malaria.

Disclosed herein are methods, systems, and compositions comprising genetically modified probiotic microorganisms. In some embodiments, the genetically modified probiotic microorganisms produce at least one viral coat protein and/or at least one fusion protein comprising an antigenic polypeptide linked to a viral coat protein.

The present invention features a method and kit for isolating microvesicles or extracting microvesicle nucleic acids from a biological sample by using a control particle. The present invention provides control particles that are viruses or virus-like particles, such as bacteriophages, that contain control nucleic acids that can be detected to assess the accuracy, reliability, and efficiency of the microvesicle isolation or nucleic acid extraction steps. The methods described herein may further comprise the analysis of the presence, absence, or level of at least one biomarker associated with a disease or medical condition for diagnosing, prognosing, or monitoring the disease or medical condition.

Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

A lentiviral vector and a method for delivering an exogenous RNA by the lentiviral vector are provided. The lentiviral vector is prepared by transfecting plasmids containing a genome sequence of the lentiviral vector into a virus-producing cell, collecting a supernatant and concentration. Specifically, according to the principle of combining an RNA-binding protein with an RNA sequence identified by the RNA-binding protein, the RNA-binding protein is integrated into a skeleton of a lentivirus GagPol long-chain protein, and the RNA sequence identified by the RNA-binding protein is connected to the exogenous target RNA, so that the exogenous target RNA is packaged into lentiviral particles during the assembly of the lentiviral particles. The exogenous target RNA can be mRNA, gRNA or RNA with other functions. The present invention can be used in the fields of gene editing, gene therapy, cell therapy, immunotherapy, regenerative medicine and basic biology.

Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

Provided are compositions, systems, and methods useful for effecting gene editing in eukaryotic cells. Compositions include plasmids that encode one or more viral fusion proteins in which one or more viral proteins are fused with an aptamer-binding protein. Compositions also include plasmids that encode a non-viral nucleic acid sequence, wherein the non-viral nucleic acid sequence encodes a CRISPR system component. In some instances, the non-viral nucleic acid sequence also includes an aptamer sequence. The plasmids can be used to generate viral particles, including lentivirus-like particles that contain a viral fusion protein and a non-viral RNA sequence. Systems of producing such viral particles are provided. Also provided are methods of using the viral particles of the disclosure to effect gene editing in eukaryotic cells.

The invention provides methods and compositions for improved production of large quantities of unencapsidated double strand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phosporibosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA.

Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein.

An immunogen generally includes a virus-like particle and an antigen linked to the virus-like particle. The antigen includes an antigenic portion of a polypeptide, wherein the polypeptide inhibits lipoprotein lipase (LPL) activity by binding to LPL. In some embodiments, the polypeptide is at least a portion of angiopoietin-like 3 (ANGPTL3). In other embodiments, the polypeptide is at least a portion of angiopoietin-like 4 (ANGPTL4). In other embodiments, the polypeptide at least a portion of angiopoietin-like 8 (ANGPTL8). In some embodiments, the virus-like particle is a Qbeta immunogenic carrier. In some of these embodiments, the antigen is linked to the virus-like particle through a Gly-Gly-Gly-Cys linker at the C-terminal of the antigen.