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Table 2 Comparisons of reprogramming delivery system

From: Understanding the molecular basis of autism in a dish using hiPSCs-derived neurons from ASD patients

  Delivery system Pros Cons References
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]