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Among the many promising possibilities of using CRISPR-based therapeutics, their translational use in monogenic human genetic diseases has the potential to provide long-term therapy after a single treatment. Genetic disorders can be treated with the help of CRISPR by editing the defective (disease-causing) gene or by editing the enhancer or regulator of the defective gene. Numerous studies, which are summarized in the table below (Table ), have shown promising results by using these two approaches.

3. Examples of CRISPR-Based Therapeuticsfor the Treatment of Genetic Disorders.

DiseaseCRISPR targetapproachmajor outcome of the studyreferenceDuchenne muscular dystrophydystrophin gene (DMD)single or multiplexed sgRNAs were developedto restore thedystrophin reading frame by targeting the mutational hotspot at exons45–55 and introducing shifts within exons or deleting one ormore exonsdystrophin expression is restored in vitroOusterout et al. Huntington’sdiseaseHuntingtin gene (HTT)HTT 5′ UTR was targetedimpropermaturation of the transcript and reducing the expressionof the disease-causing alleleKolli et al.a dual sgRNA approachwas used in vitro toexcise a 44kb promoter region upstream of a mutant HTT gene to silence its expressionexpression of the Huntington’sdisease-causing variant wasablatedShin et al.glaucomamyocilin gene (MYOC)Knocked down the expression of mutant MYOC in a mouse model of primary open-angle glaucomareductionof ER stress, lower intraocular pressure, and thepreventability of further glaucomatous damage in mouse eyes was observed. The authors also demonstrated the feasibility of utilizing CRISPR/Cas9in human eyes with glaucomaJain et al.hereditary tyrosinemiatype Ifumarylacetoacetate hydrolase gene (FAH)HDR-mediated point mutation correction in mouse hepatocytes.a significant proportion of alleles were correctedVanLith et al. Leber congenital amaurosis type 10 (LCA10)centrosomalprotein 290 gene (CEP290)AAV5-basedtherapy (EDIT-101) encapsulates Staphylococcusaureus Cas9 (SaCas9) and two sgRNAs targeting genomic locationsupstream and downstream of the intronic CEP290 pointmutation. The two sgRNAs enable cutting around the mutation to induceits removal or inversionnormal splicing of CEP290 pre-mRNA was restoredMaeder et al. Noonan syndromeleucine zipper like post translational regulator 1 gene (LZTR1)intron 16 of LZTR1 was targetedthe gene editing process could overcomethe disease phenotypeassociated with Noonan syndrome-associated cardiomyopathy in iPSC-derivedcardiomyocytes in vitroHanses et al. Angelman syndromeUBE3A-ATS Inc. RNAUBE3A-ATS Inc. RNA was targetedin cultured human neurons andin a mouse model of the diseasetargeting of UBE3A-ATSablated its function, leading to expressionof the paternal UBE3A gene and rescuing the diseasephenotypeWolter et al.congenital muscular dystrophy type 1A (MDC1A)laminin subunit alpha 1 gene (LAMA1)CRISPR activator mediated gene upregulation3.6-foldupregulation of LAMA1 was observedKemaladevi et al.genetic deafnesstransmembrane channel like 1gene (TMC1)non-homologous end joining(NHEJ)-mediated mutant Tmc alleledisruptiondeafness was prevented in mouse models upto one year postinjectionGyörgy et al.