PMID- 12130492 OWN - NLM STAT- MEDLINE DCOM- 20020906 LR - 20211103 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 100 IP - 3 DP - 2002 Aug 1 TI - Lentiviral vectors pseudotyped with a modified RD114 envelope glycoprotein show increased stability in sera and augmented transduction of primary lymphocytes and CD34+ cells derived from human and nonhuman primates. PG - 823-32 AB - Generating lentiviral vectors pseudotyped with different viral glycoproteins (GPs) may modulate the physicochemical properties of the vectors, their interaction with the host immune system, and their host range. We have investigated the capacity of a panel of GPs of both retroviral (amphotropic murine leukemia virus [MLV-A]; gibbon ape leukemia virus [GALV]; RD114, feline endogenous virus) and nonretroviral (fowl plague virus [FPV]; Ebola virus [EboV]; vesicular stomatitis virus [VSV]; lymphocytic choriomeningitis virus [LCMV]) origins to pseudotype lentiviral vectors derived from simian immunodeficiency virus (SIVmac251). SIV vectors were efficiently pseudotyped with the FPV hemagglutinin, VSV-G, LCMV, and MLV-A GPs. In contrast, the GALV and RD114 GPs conferred much lower infectivity to the vectors. Capitalizing on the conservation of some structural features in the transmembrane domains and cytoplasmic tails of the incorporation-competent MLV-A GP and in RD114 and GALV GPs, we generated chimeric GPs encoding the extracellular and transmembrane domains of GALV or RD114 GPs fused to the cytoplasmic tail (designated TR) of MLV-A GP. Importantly, SIV-derived vectors pseudotyped with these GALV/TR and RD114/TR GP chimeras had significantly higher titers than vectors coated with the parental GPs. Additionally, RD114/TR-pseudotyped vectors were efficiently concentrated and were resistant to inactivation induced by the complement of both human and macaque sera, indicating that modified RD114 GP-pseudotyped lentiviral vectors may be of particular interest for in vivo gene transfer applications. Furthermore, as compared to vectors pseudotyped with other retroviral GPs or with VSV-G, RD114/TR-pseudotyped vectors showed augmented transduction of human and macaque primary blood lymphocytes and CD34+ cells. FAU - Sandrin, Virginie AU - Sandrin V AD - Vectorologie Retrovirale & Therapie Genique, U412 INSERM, IFR 74, Ecole Normale Superieure de Lyon, Lyon, France. FAU - Boson, Bertrand AU - Boson B FAU - Salmon, Patrick AU - Salmon P FAU - Gay, Wilfried AU - Gay W FAU - Negre, Didier AU - Negre D FAU - Le Grand, Roger AU - Le Grand R FAU - Trono, Didier AU - Trono D FAU - Cosset, Francois-Loic AU - Cosset FL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD34) RN - 0 (Viral Envelope Proteins) SB - IM MH - Animals MH - Antigens, CD34/*blood MH - Blood Cells/*metabolism MH - Drug Stability MH - Genetic Vectors/*genetics/standards MH - Hematopoietic Stem Cells/metabolism MH - Humans MH - Lentivirus/*genetics MH - Lymphocytes/immunology/metabolism MH - Macaca MH - Simian Immunodeficiency Virus/*genetics MH - Transduction, Genetic/*methods MH - Viral Envelope Proteins/*genetics EDAT- 2002/07/20 10:00 MHDA- 2002/09/07 10:01 CRDT- 2002/07/20 10:00 PHST- 2002/07/20 10:00 [pubmed] PHST- 2002/09/07 10:01 [medline] PHST- 2002/07/20 10:00 [entrez] AID - S0006-4971(20)59380-4 [pii] AID - 10.1182/blood-2001-11-0042 [doi] PST - ppublish SO - Blood. 2002 Aug 1;100(3):823-32. doi: 10.1182/blood-2001-11-0042.