Abstract: A method is provided for producing a recombinant pseudotyped viral vector particle wherein a cell is transfecting with (i) at least one vector construct; (ii) at least one packaging construct; and (iii) an expression construct encoding a chimeric glycoprotein encoded by a nucleic acid comprising the sequence of SEQ ID NO: 1 to yield a producer cell, followed by culturing the producer cell in a medium; and separating the producer cell from the medium to recover the recombinant viral vector particle from the medium. Vectors obtained in this manner have significantly higher titers than vectors coated with the parental non-chimeric glycoprotein.

Abstract: The present invention provides improved chimeric glycoproteins (GPs) and improved lentiviral vectors pseudotyped with those glycoproteins. Also provided are methods and compositions for making such glycoproteins and vectors, and improved methods of in vitro and in vivo transduction of cells with such vectors. Improved chimeric GPs encode the extracellular and transmembrane domains of GALV or RD114 GPs fused to the cytoplasmic tail of MLV-A GP. Vectors pseudotyped with these GAL V/TR and RD 114/TR GP chimeras have significantly higher titers than vectors coated with the parental GPs. Additionally, RD114/TR-pseudotyped vectors are efficiently concentrated and are resistant to inactivation induced by the complement of both human and macaque sera. RD114 GP-pseudotyped lentiviral vectors have particular utility for in vivo gene transfer applications.

Abstract: The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise promoters active to promote expression specific to cell types or tissues. Further, promoters are providing that are amenable to control by activators, enhancers, or repressors. These vectors are in a self-inactivating configuration for biosaftey. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element, without any decrease in the specificity or control exerted by the promoters.