Method for expression of heterologous proteins using a recombinant negative-strand rna virus vector

An in vitro method of reprogramming an at least partially differentiated cell to a less differentiated cell or programming a cell to be programmed to a desired differentiated state, the method comprising:

• (a) providing an at least partially differentiated cell or a cell to be programmed from a donor,
• (b) introducing at least one heterologous nucleic acid sequence into the cell provided in step (a) by infecting the cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector comprises a viral genome coding for a P protein having a mutation, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and
• (c) culturing the infected cell under conditions effective to express said at least one heterologous nucleic acid sequence,
• wherein said at least one heterologous nucleic acid sequence encodes a cellular reprogramming or programming factor.

An in vitro method of treating a genetic disorder, the method comprising:

• (a) providing a cell from a donor,
• (b) introducing at least one heterologous nucleic acid sequence into the cell provided in step (a) by infecting the cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector comprises a viral genome coding for a P protein having a mutation, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and
• (c) culturing the infected cell under conditions effective to express said at least one heterologous nucleic acid sequence and/or to allow the cell to expand,
• wherein said at least one heterologous nucleic acid sequence encodes a therapeutic protein capable of treating said genetic disorder.