Overview of Delivery Technologies for Molecular Determinants in Neuronal Reprogramming

Abstract

Cellular reprogramming is the conversion of a cell into another cell type by the forced expression of cell-lineage transcription factors. One example of cellular reprogramming is direct neuronal reprogramming, in which neurons or other neuronal cells are directly converted from fibroblasts or astrocytes. These induced neurons have significant potential for research and therapeutic applications, such as in cell replacement therapy. However, current delivery strategies of conversion factors have fundamental limitations. In this review, we outlined the current used delivery technologies in neuronal reprogramming and their limitations and advantages. The first employed delivery strategies were mainly viral systems, such as lentiviruses or adeno-associated viruses, yet these systems cause major safety concerns, including risk for insertional mutagenesis and inflammation. Several non-viral delivery systems, among which are physical and chemical methods, have been investigated as well. However, these systems exert inferior reprogramming efficiency. Emerging delivery technologies, such as lipid-based nanoparticles or particles derived by combinations of delivery materials, could provide new opportunities in safe and effective delivery for neuronal reprogramming. Employing target specific and efficient engineered delivery systems is essential to proceed neuronal reprogramming into clinical practice.