Table 2 Comparisons of reprogramming delivery system

Integrating method

Retrovirus

High reprogramming efficiency (~0.01–0.1 %)

Possibility of oncogenesis; silencing of functional genes

Takahashi and Yamanaka. 2006 [32]

Lentivirus

High reprogramming efficiency (~0.01–0.1 %)

Possibility of oncogenesis; silencing of functional genes

Yu et al. 2007 [51]

Non-integrating method

Sendai virus

No risk of altering the host genome; high reprogramming efficiency(~1 %); easy to select iPSCs

Stringent steps to remove the reprogrammed cells of replicating virus; sensitivity of the viral RNA replicase

Fusaki et al. 2009 [55]

Adenovirus

Transient, high-level expression

Low reprogramming efficiency (0.0001-0.001 %); possibility of small pieces insertion of adenoviral DNA; 3 out of 13(or approximately 23 %) were tetraploid

Stadtfeld et al. 2008 [56]

OriP/EBNA-based episomal vector

Unnecessary for viral packaging; gradual loss of cellular EV without drug selection; relatively high reprogramming efficiency of IRES2-mediated expression(~0.1 %); further addition of c-Myc and Klf4 improve the reprogramming efficiency to over 1 %

Unstable transfection efficiency

Yu et al. 2009 [168]

Piggy BAC transposons

Technical simplification (use of effortless plasmid DNA preparation and commercial transfection products); no limited range of somatic cell types for reprogramming; allow the option of xeno-free hiPSC production; accurate transgene removal through transposase expression

Labor intensive removal of multiple transposons; more CNVs in early passage than in intermediate passage;

Woltjen et al. 2009 [59]; Hussein et al. 2011 [162]

Cre-inducible/excisable lentivirus

Minimize the risk of chromosomal translocations; improve the developmental potential and differentiation capacity

Inefficient delivery of Cre; difficult to detect successful Cre-recombeniation; result in mosaic colonies; leaves 200 bp of exogenous DNA

Sommer et al. 2010 [58]; Soldner et al. 2009 [169]; Papapetrou et al. 2011 [170]

Minicircle DNA

Free of foreign or chemical elements; requiring only a single vector without the need for subsequent drug selection, vector excision, or the inclusion of oncogenes; FAD approved

Low reprogramming efficiency (~0.005 %)

Jia et al. 2010 [73]; Narsinh et al. 2011 [75]

Poly-arginine-tagged polypeptide

No risk of altering the host genome; simpler and faster approach than the genetic method

Low reprogramming efficiency (~0.006 %); requires either chemical treatment or greater than four rounds of treatment; expertise in protein chemistry and handling

Zhou et al. 2009 [171]; Kim et al. 2009 [60]

RNA-modified synthetic mRNA

Avoid the endogenous antiviral cell defense; high efficiency of over 2 %; resultant iPSC colonies emerge as early as 17 days

Labor intensive repeated transfection

Warren et al. 2010 [61]

Non-immunogenic; cost-effective; easily handled;

Relatively low and inconsistent efficiency

Hou et al. 2013 [80]