Abstract: The invention provides novel retroviral vectors that have enhanced transcription termination structures. The termination structures comprise one or several heterologous upstream transcription termination enhancer (UE) sequences, or one or more additional copies of endogenous UE sequences operably associated with the 3′ LTR polyadenylation signal. The retroviral vectors of the invention have various improved properties over conventional vectors, including stronger gene expression, enhanced vector titer and reduced interference with host cell gene expression resulting from read-through of vector initiated transcriptional events.

Abstract: The invention provides novel retroviral vectors that have enhanced transcription termination structures. The termination structures comprise one or several heterologous upstream transcription termination enhancer (UE) sequences, or one or more additional copies of endogenous UE sequences operably associated with the 3′ LTR polyadenylation signal. The retroviral vectors of the invention have various improved properties over conventional vectors, including stronger gene expression, enhanced vector titer and reduced interference with host cell gene expression resulting from read-through of vector initiated transcriptional events.

Abstract: A method of making retrovirus vectors having selected characteristics, in particular an increased ability to infect a particular target cell, comprises subjecting a starting retrovirus or retroviral vector to a selection process in vitro which involves a plurality of rounds of infection of a host cell during which the retrovirus or retroviral vector evolves to attain the selected characteristics. Components of the evolved retrovirus or retroviral vector can be used in retroviral vector production systems for producing retroviral vectors having the selected characteristics. The invention is particularly useful for preparing retroviral vectors suitable for gene therapy.

Abstract: A DNA construct is disclosed which comprises a packagable retroviral genome operably linked to a first promotor, wherein the retroviral genome comprises a 5' long terminal repeat (5' LTR) which includes sequences encoding R and U3 regions and 3' long terminal repeat (3' LTR) which includes sequences encoding R and U3 regions, and wherein at least said R regions of the 5' LTR and 3' LTR are identical to each other and are different from those of the retrovirus on which the retroviral genome is based. The DNA constructs are useful in the production of packaged retroviruses.