Vectofusin-1, a New Viral Entry Enhancer, Strongly Promotes Lentiviral Transduction of Human Hematopoietic Stem Cells

• Published in: Molecular therapy. Nucleic acids 2013, Vol.2 (5), p.e90-e90, Article e90
• Main Authors: Fenard, David, Ingrao, Dina, Seye, Ababacar, Buisset, Julien, Genries, Sandrine, Martin, Samia, Kichler, Antoine, Galy, Anne
• Format: Article
• Language: English
• Subjects: cationic peptide; gene therapy; hematopoietic stem cell; Human immunodeficiency virus; Human immunodeficiency virus 1; lentiviral vector; Methods - Original
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1038/mtna.2013.17

Gene transfer into hCD34+ hematopoietic stem/progenitor cells (HSCs) using human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) has several promising therapeutic applications. Yet, efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist such as fibronectin fragments and cationic compounds, but all present limitations. In this study, we describe a new transduction enhancer called Vectofusin-1, which is a short cationic peptide, active on several LV pseudotypes. Vectofusin-1 is used as a soluble additive to safely increase the frequency of transduced HSCs and to augment the level of transduction to one or two copies of vector per cell in a vector dose-dependent manner. Vectofusin-1 acts at the entry step by promoting the adhesion and the fusion between viral and cellular membranes. Vectofusin-1 is therefore a promising additive that could significantly ameliorate hCD34+ cell-based gene therapy.