Integrating Gene Correction in the Reprogramming and Transdifferentiation Processes: A One-Step Strategy to Overcome Stem Cell-Based Gene Therapy Limitations

Figure 2

Overview of the combined reprogramming and gene-correction strategy. (a) Current iPSC-based gene-correction approach. Step a: nonpathogenic iPSCs can stably maintain their self-renewal property. Step b: pathogenic iPSCs, derived from cells with mutations in ATM, FA, LIG4, or ACVR1, exhibit restrictive self-renewal and a potential rise of genome instability, hampering progress to Step b. Step a: the iPSCs generated from Step a can be subsequently subject to gene correction with various tools such as ZFNs, TALENs, CRISPR/Cas9, or BAC vectors. (b) A one-step process involving simultaneous reprogramming and gene correction. Gene-corrected iPSCs are directly produced from patient-derived somatic cells, concurrently combining the reprogramming factors and gene-correction tools.

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(b)