Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

A method of making a pharmaceutical composition comprising producing a recombinant lentivirus and combining it with a pharmaceutically acceptable excipient, wherein the producing step comprises:

• (a) transfecting a suitable packaging host cell with the following vectors:
• (i) a first vector providing a nucleic acid encoding a lentiviral gag and a lentiviral pol, where the gag and pol nucleic acid sequences are operably linked to a heterologous regulatory nucleic acid sequence and where the first vector is defective for nucleic acid sequence encoding functional env protein and devoid of lentiviral sequences both upstream and downstream from a splice donor site to a gag initiation site of a lentiviral genome;
• (ii) a second vector providing a nucleic acid encoding a non-lentiviral env protein;
• and
• (iii) a third vector providing a nucleic acid sequence containing a lentiviral packaging signal flanked by lentiviral cis-acting nucleic acid sequences for reverse transcription and integration, a heterologous nucleic acid sequence operably linked to a regulatory nucleic acid sequence, and a nucleic acid sequence encoding an intercellular trafficking signal, wherein the nucleic acid sequence encoding the intercellular trafficking signal is fused in-frame with the heterologous nucleic acid sequence, and wherein the third vector does not contain a complete gag, pol, or env gene;
• and
• (b) recovering the recombinant lentivirus.