The present application relates to arenavirus particles containing a genome engineered such that an arenaviral open reading frame (“ORF”) is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high-level transgene expression. In certain embodiments, the arenavirus particles are tri-segmented. In particular, described herein is a nucleotide sequence comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. Also described herein is an arenavirus particle containing a genome engineered such that an arenaviral ORF is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. Also described herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. The arenavirus particles described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

Provided herein are genetically engineered Pichinde viruses that include three ambiense genomic segments. The first genomic segment includes two coding regions encoding a Z protein and a L RdRp protein. The second genomic segment includes a coding region encoding a nucleoprotein (NP) and the third genomic segment includes a coding region encoding a glycoprotein. Each of the second and third genomic segments include an additional coding region that may encode a reovirus sigma C protein or a reovims sigma B protein. In one embodiment, a genetically engineered Pichinde virus encodes a reovims sigma C protein and a reovirus sigma B protein. Also provided herein is a reverse genetics system for making genetically engineered Pichinde virus, and a collection of vectors that can be used to produce genetically engineered Pichinde virus. Further provided are methods for using a reverse genetics system, and methods for treating a reovirus infection in a subject.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

The present application relates to Pichinde viruses with rearrangements of their open reading frames (“ORF”) in their genomes. In particular. described herein is a modified Pichinde virus genomic segment, wherein the Pichinde virus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented Pichinde virus particles comprising one L segment and two S segments or two L segments and one S segment. The Pichinde virus, described herein may be suitable for vaccines md/or treatment of diseases and/or for the use in immunotherapies.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

The present application relates to Pichinde viruses with rearrangements of their open reading frames (ORF) in their genomes. In particular, described herein is a modified Pichinde virus genomic segment, wherein the Pichinde virus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented Pichinde virus particles comprising one L segment and two S segments or two L segments and one S segment. The Pichinde virus, described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.