Delivery Systems in Neuronal Direct Cell Reprogramming

Neuronal direct cell reprogramming approach allows direct conversion of somatic cells into neurons via forced expression of neuronal cell-lineage transcription factors (TFs). These so-called induced neuronal cells have significant potential as research tools and for therapeutic applications, such as in cell replacement therapy. However, the optimization of TF delivery strategies is crucial to reach clinical practice. In this review, we outlined the currently explored delivery technologies in neuronal direct cell reprogramming and their limitations and advantages. The first employed delivery strategies were mainly integrating viral systems, such as lentiviruses that exert consistently high transgene expression in most cell types. On the other hand, viral systems cause major safety concerns, including the risk for insertional mutagenesis and inflammation. More recently, several safer nonviral delivery systems have been investigated as well; however, these systems generally exert inferior reprogramming efficiency compared with viral systems. Emerging delivery technologies could provide new opportunities in the achievement of safe and effective delivery for neuronal direct cell reprogramming.