Table 1.

Comparison of Delivery Methods of Reprogramming Factors for Cell Reprogramming

methods	biological	physical	chemical
advantages	applicable both in vitro and in vivo	applicable in vitro	applicable both in vitro and in vivo, ease of administration
	high transfection efficiency	nonimmunogenic and no mutagenesis, low or no genetic integration	nonimmunogenic and no mutagenesis, no genetic integration
	works well for difficult-to-transfect cells	deliver diverse cargos without size limitations	deliver diverse cargos without size limitations
		rapid, instantaneous transfection	diverse biomaterials are available or can be specifically designed
			targeted delivery and controlled release
limitations	limited to nucleic acid delivery	less amenable to in vivo translation	low efficiency and slow delivery
	limited packaging capacity	loss of cytoplasmic content	carrier materials may perturb cell function and/or cause toxicity in unpredictable ways
	nonspecific target delivery in vivo	some approaches (e.g., bulk electroporation) can lead to excessive cell damage, highly stochastic transfection, and low efficiency	complex, laborious, and expensive material synthesis is required for advanced smart carriers
	time-consuming, laborious, expensive and technically challenging	requires special expertise and complex fabrication protocols to achieve dose control
	biosafety issues related to cytotoxicity, mutagenesis for integrating viruses, and adverse host immune response