The present disclosure provides a system for the expression of target protein in conjunction with enhancer protein. The enhancer protein may be a viral protein that blocks nucleocytoplasmic transport. Also provided are polynucleotides, vectors, and cells comprising target protein and enhancer protein nucleic acid sequences.

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynuclotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

The present disclosure provides a system for the expression of target protein in conjunction with enhancer protein. The enhancer protein may be a viral protein that blocks nucleocytoplasmic transport. Also provided are polynucleotides, vectors, and cells comprising target protein and enhancer protein nucleic acid sequences.

Provided for herein are fusogenic rhabdovirus glycoproteins and uses thereof, compositions comprising the same, and methods of using the same. Also provided for herein are pseudotyped viral particles comprising rhabdovirus glycoproteins as provided for herein and targeting moieties as provided for herein. Also provided are methods of generating and using the pseudotyped viral particles as provided for herein.

The present invention relates to exosomes, loaded with genetic material and methods of producing them and to the use of such exosomes for delivering genetic material in vivo, in particular the use of such exosomes in methods of gene therapy or gene silencing.

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

The present invention relates to exosomes, loaded with genetic material and methods of producing them and to the use of such exosomes for delivering genetic material in vivo, in particular the use of such exosomes in methods of gene therapy or gene silencing.

The invention includes systems, methods, and compositions for designing secreted fusogenic ectosome vesicles, or gectosomes, that selectively encapsulate specific target proteins, nucleic acids and/or other small molecules in a predetermined manner. These engineered gectosomes can be used to deliver desired cargos to receipt cells in vitro, ex vivo, or in vivo and may further reprogram target cellular phenotypes in a dose-dependent manner, as well as perform genome editing functions, among others.