Production of Retroviral Vectors: Review

Ana      S. Coroadinha; Leonor      Gama-Norton; Ana      I. Amaral; Hansjorg      Hauser; Paula      M. Alves; Pedro      E. Cruz

Abstract

Retroviral vectors are presently amongst the most widely used vectors in gene therapy clinical trials to target pathologies of different origins, such as cancers, genetic diseases or neurological disorders. This review provides an overview on the evolution of retroviral vector design and production for gene therapy applications, including state of the art developments in flexible producer cells and safe vectors. In addition, production and purification processes will be addressed, with a particular focus on the improvements undertaken to increase vector productivity and to reduce the rapid loss of infectivity, which presently represent the main challenges in retroviral vectors production for gene therapy.

Keywords: Packaging cells, production, purification, retrovirus, Murine leukaemia virus (MLV), hematopoetic stem cells, MLV LTR, MLV SIN vectors, Retroviridae family, oncoretroviruses, Moloney Murine Leukemia Viruses, Simian Foamy Virus - SFV, reverse transcriptase (RT), integrase (IN), Matrix (MA) proteins, envelope glycoproteins, gag (group specific antigen), pro (PR), pol (polymerase), env (envelope), MA, CA, NC, LTRs (long terminal repeats), replication-competent retroviruses (RCRs), avian, simian, feline, SV40, PA317, AM, CRIP, Gp envAm12, PG13, HAII, FLY A4, FLY RD18, Te Fly Ga18, Te Fly A, CEM FLY, 293-SPA, Phoenix, Flp293, 293 FLEX, PG368, vesicular stomatitis virus glycoprotein G (VSV-G), biotin-streptavidin bridges, Rous Sarcoma Virus (RSV) promoter, Spleen Focus Forming Virus (SFFV) U3 sequence, IVIM assay, NIH/3T3, galactosyl(1-3)galactosyl carbohydrate moieties, Metastic Breast Cancer, Glioblastoma, HIV infection, SCID-X1, Cronic Granulatomous disease, Hemophilia A, Hyclone/Thermo, Excellerex, ATMI/Guerin, GE, Sartorius, streptavidin-biotin affinity, trehalose, cryoprotectants, adenosine deaminase deficiency (ADA), X-CGD, CD34 cells, Gp91 phox gene, Gaucher disease, glucocerebrosidades gene, hypercholesterolemia, low-density lipoprotein receptor, melanom, Renal Cancer, Neuroblastoma, Recurrent High-Grade Gliomas, Wiskott-Aldrich- Syndrome, Peripheral artery disease, Multiple Sclerosis, Anti-PSMA-Zeta T cell receptor, CD19-specific Zeta T cell receptor, HER2-neu-Specific scFvFc-Zeta T Cell Receptor, E. coli cytosine deaminase, T-cell receptor specific for Wilms tumour antigen 1, Vascular endothelial growth factor (VEGF) Fibulin-5, Myelin Basic Protein (hMBP)