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

Figure 3

Application of the gene-correction approach in cells with the LRRK2 (G2019S) mutation. (a) Conventional gene-correction approach using mutant iPSCs generated from LRRK2 (G2019S) mutant fibroblasts, involving reprogramming with subsequent gene correction (Step via Step a), and the combined reprogramming and gene-correction approach based on LRRK2 (G2019S) mutant fibroblasts (Step b). (b) Mutant iNSCs are generated from LRRK2 (G2019S) mutant fibroblasts, potentially exhibiting impaired self-renewal or proliferation in Step a, whereas, in Step b, transdifferentiation and gene correction occur simultaneously and the corrected iNSCs are capable of stable proliferation with maintained self-renewal potential.

(a)

(b)