ABSTRACT
Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV.G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types.
Subject(s)
Antigen-Presenting Cells , Gene Targeting/methods , Genetic Vectors , Lentivirus/genetics , Macrophages , Single-Domain Antibodies , Animals , Gene Transfer Techniques , Humans , Mice , Transduction, GeneticABSTRACT
Although the busy rural GP may have special needs and particular difficulties with regard to CME, there are a number of ways of meeting these needs and surmounting the barriers. Continuing feedback from those 'at the coal face' is a vital part of this process. Please contact the QA and CE Unit in your RACGP Faculty office if you need help or have a point of view to express. The Program can only improve with the full participation of all GPs with a QA and CE requirement.
