Engineering lentiviral vectors for gene delivery

The development of lentiviral vectors to deliver genes to specific cell types are useful tools because they have the ability to produce stable transduction, maintain long-term transgene expression, and transduce both dividing and non-dividing cells. Despite the high transduction efficiency of lentiviral vectors, their tropism frequently does not match the desired gene delivery application. We report herein, strategies to modify lentiviral vectors using diverse techniques which allow targeting gene delivery to specific cell types. To target CD117 expressing cells we engineered a lentivector that incorporates membrane-bound human stem cell factor (hSCF), and for fusion, a Sindbis virus-derived fusogenic molecule (FM) onto the lentiviral surface. Lentiviral vectors pseudotyped with envelope proteins of alphaviruses have recently attracted considerable interest for their potential utilization for immunotherapy due to their capacity to transduce dendritic cells. We report lentiviral vectors pseudotyped with envelope glycoproteins derived from the Aura, Sindbis and Semliki Forest alphaviruses have a natural capacity to transduce dendritic cells through the DC-SIGN receptor. Finally, in this study, we explore the ability of pseudotyped lentiviral vectors with envelope glycoproteins derived from a neuroadapted Sindbis virus envelope glycoprotein to specifically transduce neuronal cell types. The development of engineered lentiviral vectors to achieve targeted transduction while avoiding transduction of non-target cells will be important tools for future gene delivery implementation in a wide range of fields.