Reprogramming somatic cells to iPS cells
| Vector type | Cell types | Factors * | Efficiency (%) | Advantages | Disadvantages | |
|---|---|---|---|---|---|---|
|
*OSKM and similar factor names represent combinations of reprogramming factors: K, KLF4; L, LIN28; M, c-MYC; N, NANOG; O, OCT4; S, SOX2; and VPA, valproic acid. |
||||||
| Integrating | Retroviral1, 14, 82, 83 | Fibroblasts, neural stem cells, stomach cells, liver cells, keratinocytes, amniotic cells, blood cells and adipose cells | OSKM, OSK, OSK + VPA, or OS + VPA | ~0.001–1 | Reasonably efficient | Genomic integration, incomplete proviral silencing and slow kinetics |
| Lentiviral15, 16, 84, 85 | Fibroblasts and keratinocytes | OSKM or miR302/367 cluster + VPA | ~0.1–1.1 | Reasonably efficient and transduces dividing and non-dividing cells | Genomic integration and incomplete proviral silencing | |
| Inducible lentiviral23, 28 | Fibroblasts, β cells, keratinocytes, blood cells and melanocytes | OSKM or OSKMN | ~0.1–2 | Reasonably efficient and allows controlled expression of factors | Genomic integration and requirement for transactivator expression | |
| Excisable | Transposon86 | Fibroblasts | OSKM | ~0.1 | Reasonably efficient and no genomic integration | Labour-intensive screening of excised lines |
| loxP-flanked lentiviral87 | Fibroblasts | OSK | ~0.1–1 | Reasonably efficient and no genomic integration | Labour-intensive screening of excised lines, and loxP sites retained in the genome | |
| Non-integrating | Adenoviral88, 89 | Fibroblasts and liver cells | OSKM | ~0.001 | No genomic integration | Low efficiency |
| Plasmid90, 91 | Fibroblasts | OSNL | ~0.001 | Only occasional genomic integration | Low efficiency and occasional vector genomic integration | |
| DNA free | Sendai virus92 | Fibroblasts | OSKM | ~1 | No genomic integration | Sequence-sensitive RNA replicase, and difficulty in purging cells of replicating virus |
| Protein93, 94 | Fibroblasts | OS | ~0.001 | No genomic integration, direct delivery of transcription factors and no DNA-related complications | Low efficiency, short half-life, and requirement for large quantities of pure proteins and multiple applications of protein | |
| Modified mRNA95 | Fibroblasts | OSKM or OSKML + VPA | ~1–4.4 | No genomic integration, bypasses innate antiviral response, faster reprogramming kinetics, controllable and high efficiency | Requirement for multiple rounds of transfection | |
http://www.nature.com/nature/journal/v481/n7381/fig_tab/nature10761_T1.html
