Virus particles for therapeutic purposes
The invention relates to a virus particle comprising a lymphocytic choriomeningitis virus (LCMV) S segment and an LCMV L segment, wherein the S segment comprises an open reading frame encoding a glycoprotein derived from LCMV strain WE, and wherein the L segment comprises an open reading frame encoding an L protein derived from LCMV strain Clone13. The invention also relates to related host cells, methods of producing such virus particles, pharmaceutical compositions comprising such virus particles, and medical uses of such virus particles.
1 . A virus particle comprising:
a lymphocytic choriomeningitis virus (LCMV) S segment nucleic acid comprising an open reading frame encoding an LCMV glycoprotein having at least 99% sequence identity to SEQ ID NO: 14, and an open reading frame encoding an LCMV nucleoprotein having at least 99% sequence identity to SEQ ID NO: 6, wherein the open reading frame encoding the LCMV glycoprotein encodes a tryptophan at residue 185 and a methionine at residue 181 of the LCMV glycoprotein; and
an LCMV L segment nucleic acid comprising an open reading frame encoding an LCMV L protein of SEQ ID NO: 40, and an open reading frame encoding an LCMV Z protein of SEQ ID NO: 38.
2 . The virus particle of claim 1 , wherein the virus particle is less pathogenic in a mouse compared to LCMV strain WE.
3 . The virus particle of claim 1 , wherein the virus particle shows increased replication in tumor cells compared to LCMV strain WE.
4 . The virus particle of claim 1 , wherein the virus particle shows reduced replication in a healthy organ compared to LCMV strain WE and/or a virus particle comprising the same S segment as the virus particle and an L segment as shown in SEQ ID NO: 2.
5 . The virus particle of claim 1 , wherein the virus particle has a bi-segmented genome.
6 . The virus particle of claim 1 , wherein the virus particle is an arenavirus particle.
7 . A host cell line, wherein cells of the host cell line comprise an LCMV S segment and an LCMV L segment of claim 1 .
8 . A host cell line, wherein cells of the host cell line comprise cDNA of an LCMV S segment and an LCMV L segment of claim 1 .
9 . A pharmaceutical composition comprising a virus particle of claim 1 .
10 . The virus particle of claim 1 , wherein the open reading frame encoding an LCMV glycoprotein has at least 99.7% % sequence identity to SEQ ID NO: 14, and the open reading frame encoding an LCMV nucleoprotein has at least 99.7% sequence identity to SEQ ID NO: 6.