Gene delivery system and method of use

A recombinant replication competent mammalian retrovirus, comprising:

• an oncoretroviral polynucleotide sequence comprising:
• a nucleic acid sequence encoding a retroviral GAG protein;
• a nucleic acid sequence encoding a retroviral POL protein;
• a nucleic acid sequence encoding a retroviral envelope;
• Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ end of the oncoretroviral polynucleotide sequence;
• a cassette comprising a regulatory nucleic acid sequence operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the U3 region of the 3′ LTR and 3′ to the nucleic acid sequence encoding the retroviral envelope;
• and
• cis-acting sequences for reverse transcription, packaging and integration in a target naturally occurring mammalian cell.

A recombinant replication competent mammalian retrovirus comprising:

• a retroviral GAG protein;
• a retroviral POL protein;
• a retroviral envelope (ENV);
• a oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and/or 3′ end of the retroviral polynucleotide sequence, wherein a mammalian promoter sequence is contained within LTR sequences at the 5′ and/or 3′ end of the retroviral polynucleotide sequence, wherein the oncoretroviral polynucleotide sequence contains a coding sequence for GAG, POL and ENV;
• a cassette comprising a regulatory nucleic acid sequence operably linked to a heterologous polynucleotide, wherein the cassette is positioned 3′ to the sequence encoding the retroviral envelope and 5′ to the 3′ LTR;
• and
• cis-acting sequences necessary for reverse transcription, packaging and integration in a target cell.