Era of Genomic Medicine: A Narrative Review on CRISPR Technology as a Potential Therapeutic Tool for Human Diseases

Table 1

Application of CRISPR as a therapeutic tool for common monogenetic disorders of humans.

Disease	Manipulated gene	SgRNA target	Cell type	Species	In vivo/in vitro	Delivery	Outcome	Ref
Cystic fibrosis	CFTR locus F508 del	CFTR exon 11 or intron 11	Cultured intestinal stem cells from organoids isolated from CF patients	Human	In vitro	Cas9, sgRNA plasmid transfection	Successful and rescued CFTR protein	[28]
	F508	CFTR exon 10.	Induced pluripotent stem cells (iPSCs)	Human	In vitro	PiggyBac transposase nucleofection	Normal CFTR expression on differentiation	[29]
Sickle cell anemia	β-Globin	Exon 1 of the human β-globin gene	Blood-derived CD34^+ cells; CD34^+ stem and progenitor cells from SCA patients	Human	In vitro	Lenti-viral vector	Successful 18% gene modification in in vitro cells.; Wild; type H; b cells observed	[30]
	β-Globin		CD34^+ cells	Human	In vitro	Nucleofection	30% HDR in CD34^+ with 80% of them being viable and producing β-globin	[31]
	Glu6Val mutant gene		Stem and progenitor cells	Human	In vitro	Adeno-associated viral vector	Successful rectification achieved	[32]
Thalassemia	IV52-645	Gene targeting intron 2 mutation site near IVS2-654 C > T mutation	Thalassemia patient-derived iPSCs	Human	In vitro	PiggyBac transposon donor	Mutation corrected in the relevant site	[33]
	HBB gene CD 41/42 mutation		β-Thal iPSCs	Human	In vitro	Lenti-CRISPR V2 vector.	Cells have exhibited normal karyotype and have retained full pluripotency	[34]
	HBB mutation	TLTT deletion between 41^st and 42^nd amino acid producing Hbb gene	Naïve iPSCs obtained from urinary cells of β-thalassemic patient	Human	In vitro	pX330 vector	Exhibited normal karyotype and retained pluripotency	[35]
	HBB mutations	Exon 2	iPSCs from thalassemia patients	Human	In vitro	PiggyBac transposon vector	Full pluripotency or normal karyotypes and no off-target effects	[36]
	HBB mutations	2^nd intron of the Hbb gene.	Induced pluripotent stem cells (iPSCs)	Human	In vitro	B003 plasmid vector transfection	Normal cell types with no off-target effects	[37]
Huntington’s chorea disorder	HTT gene	Promoter region, transcription start site, and expanded CAG mutation	Primary fibroblast cells	Human	In vitro	CRISPR/Cas9 vector transfection	Rectification of mutation successful	[38]
	Mutant HTT locus	HTT exon 1 deletion	Fibroblasts and in vivo HD transgenic mice	Human and mouse	In vitro	Plasmid pX330	Rectification of mutant HTT locus	[39]
	mHTT	CAG repeats in exon 1 of the human HTT gene	HEK 239 cell line	Mouse	In vivo	Adeno-associated virus vector	Reduction in expression of mHTT in the striatum of model mice	[40]
Duchenne muscular dystrophy	Dystrophin gene	Exon 45–55 with introduced shifts within exons	Myoblast cells	Human	In vitro	hCas9-T2A vector	Single large deletions with corrections in 62% DMD	[41]
	Dystrophin gene	Exon knocking	Patient-derived iPSCs	Human	In vitro	Nuclease-expressing plasmids	Replacing dystrophin protein when differentiated into skeletal muscle	[42]
Hemophilia	F8 gene	Introns 1 and 22 of the F8 gene	Patient-derived iPSCs	Human	In vitro	Cas9- and gRNA-encoding plasmids vector	Reversal of inversion back to WT situation	[43]
	Y371D in the human F9 gene			Mouse	In vivo	Adenoviral vector transfection	Mutation rectified	[44]
Chronic granulomatous disease	CYBB gene		iPSCs derived from phagocytes from CGD patients	Human	In vitro	CRISPR-cas9 vectors	Restoration of oxidative capacity	[45]
	Gp91^phox		Patient-derived blood stem cells	Human	In vitro	Cas9 plasmid vector	Stable expression of gene following rectification and engraftment into mouse models	[46]