Efficient gene expression in neurons is indispensable for the study of neuronal cell biology, such as investigating gene and protein function, cell behavior and/or cell morphology. The need for more physiologically relevant cellular models has become a requirement to further validate studies performed in neuron cell lines that are easier to transfect compared to primary neurons. Primary neurons are fragile and difficult to transfect, and with currently available transfection method either results in low transfection efficiency or low cell viability. Currently, the most efficient methods for exogenous gene delivery into slow to non-dividing neurons are electroporation or viral-based transduction methods. These methods are often associated with side-effects on cellular viability and morphology. Here we describe the screening of a new library of chemical compounds to identify candidates as potent DNA transfection reagents in different primary neurons (such as primary hippocampal or cortical neurons from rat) and neuronal cell lines. Following the optimization of hits-to-lead, we selected the best candidate based on its high transfection efficiency and its ability to maintain excellent cell viability and morphology.

Identifying efficient chemical-based nucleic acid transfection compound for primary neurons and neuronal cell lines

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