Targeted gene delivery to CD117-expressing cells in vivo with lentiviral vectors co-displaying stem cell factor and a fusogenic molecule.
The development of a lentiviral system to deliver genes to specific cell types could improve the safety and the efficacy of gene delivery. Previously, we have developed an efficient method to target lentivectors to specific cells via an antibody-antigen interaction in vitro and in vivo. We report herein a targeted lentivector that harnesses the natural ligand-receptor recognition mechanism for targeted modification of c-KIT receptor-expressing cells. For targeting, we incorporate membrane-bound human stem cell factor (hSCF), and for fusion, a Sindbis virus-derived fusogenic molecule (FM) onto the lentiviral surface. These engineered vectors can recognize cells expressing surface CD117, resulting in efficient targeted transduction of cells in an SCF-receptor dependent manner in vitro, and in vivo in xenografted mouse models. This study expands the ability of targeting lentivectors beyond antibody targets to include cell-specific surface receptors. Development of a high titer lentivector to receptor-specific cells is an attractive approach to restrict gene expression and could potentially ensure therapeutic effects in the desired cells while limiting side effects caused by gene expression in non-target cells.
Froelich
Steven
S
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, USA.
Ziegler
Leslie
L
Stroup
Katie
K
Wang
Pin
P
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012845:Sindbis Virus / Q000235:genetics*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*; D053586:Virus Internalization
D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit