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

Table 1

Diseases with the inefficient reprogramming or inhibitory pluripotency maintenance.

Category	Disease	Gene	Gene status	Reprogramming efficiency or; pluripotency maintenance	Refs.
DNA repair	Ataxia telangiectasia (A-T)	ATM	7004delCA, 7886delTATTA	Low efficient generation (15% in heterozygote)/extremely low efficient generation (4% in homozygote)	[2]
	Fanconi anemia (FA)	FANCA, FANCD2		No reprogramming, or extremely low efficient generation (FANCA), low efficient reprogramming and poor maintenance (FANCD2)	[13, 14]
	FA or breast cancer	BRCA1, BRCA2	in exon 11 or S1598F point mutation for BRCA1, in exon 27 for BRCA2	~20-fold lower than normal	[20]
	Cancer	Rad51	Knockdown expression by shRNA	~60-fold lower than normal	[20]
	LIG4 syndrome	LIG4	c.2440C>T in allele 1 and c.1406G>A in allele 2, or c.833G>A	Low reprogramming efficiency (0.002~0.012%) and apoptosis sensitivity	[15]
Signaling	Fibrodysplasia ossificans progressiva (FOP)	ACVR1	c.617G>A	Low reprogramming efficiency (~0.05%) and inhibitory maintenance of iPSCs	[16, 17]

locus.