References | Species | Disease Model | Gene | CRISPR Construct | No. CRISPR/Cas9 microinjected zygotes | No. embryos transferred, surrogates, pregnancies | Offspring Produced | % Offspring Edited | % edited live offspring/ embryos transferred | Notable editing outcomes |
---|---|---|---|---|---|---|---|---|---|---|
C | Adrenal hypoplasia congenita, hypogonadotropic hypogonadism | DAX1* | 5 sgRNAs Cas9 mRNA | 186 | 83 29 10 | 6 live 13 miscarriage | NS* | NS* | DAX1 mutations observed in several tissues including testis Germline acquisition of edits reported by Chen et al. 2015 | |
R | Duchenne muscular dystrophy (DMD) | DMD | 2 sgRNAs Cas9 mRNA | NS | 179 59 17 | 14 live 4 stillborn 8 miscarriages | 61.1 | 5.03 | WGS revealed no off-target editing | |
Wan et al. [26] | C | Tumorigenesis | p53 | sgRNA Cas9 mRNA | 108 | 62 13 4 | 3 live 2 miscarriages | 40 | 3.2 | Biallelic editing reported in 1 live infant |
Tu et al. [25] | C | NS | ASPM | 2 sgRNAs Ubi-Cas9 mRNA | NS | 178 47 11 | 6 live | 66.7 | 2.25 | A ubiquitin-tagged Cas9 may reduce but not eliminate mosaicism |
Zuo et al. [27] | C | Paroxysmal kinesigenic dyskinesia | PRRT2 | 1 or 3 sgRNAs Cas9 mRNA | NS | 84 NS NS | 6 live 6 stillborn | 58.3 | 5.95 | A complete knock-out was produced by targeting with 3 sgRNAs |
C | Autism Spectrum Disorder | SHANK3 | 2 sgRNAs Cas9 mRNA | NS | 116 37 3 | 1 live 1 stillbirth 1 miscarriage | 100 | 0.86 | An 11.5Â kb deletion between the two targeted exons of SHANK3 detected in the miscarried fetus | |
Zhang et al. [13] | C | SIRT6-null | SIRT6 | sgRNA Cas9 mRNA | 98 | 48 12 4 | 3 live 1 miscarriage | 75 | 6.25 | Biallelic editing observed in three offspring |
Yang et al. [14] | R | Parkinson’s Disease | PINK1 | 2 sgRNAs Cas9 mRNA | 158 | 87 28 11 | 11 live 4 miscarriages | 73.3 | 5.06 | A ~ 7.2 kb deletion in PINK1 detected in three offspring |
Zhou et al. [22] | C | Autism Spectrum Disorder | SHANK3 | 2 sgRNAs | NS | 178 26 12 | 9 live 9 deceased | 55.5 (of live) | 2.80 | Three F1 edited heterozygous SHANK3-mutants confirms germline transmission of edits |
Qiu et al. [88] | C | circadian-related disorders | BMAL1 | 1–2 sgRNAs Cas9 mRNA | NS | 88 31 10 | 8 live 2 miscarriages | 60 | 6.82 | Three live knock-out infants and two mosaic generated with no off-target editing |
Tsukiyama et al. [28] | C | Polycystic kidney disease | PKD1 | sgRNA Cas9 mRNA | 403 | 86 86 29 | 14 live 8 stillbirths 7 miscarriages | 100 | 16.28 | Reported highest proportion of live edited offspring and use of an allele-specific targeting approach |
Schmidt et al. [80] | MCM | HIV-resistance | CCR5 | 2 sgRNA Cas9 RNP | NS | 50 6 0 | 0 live | 0 | 0 | Whole embryo and blastomere genotyping resulted in 23–37% bilallelic editing of CCR5 |
Chen et al. [92] | C | Parkinson’s Disease | PINK1 | 2 sgRNA Cas9-D10A mRNA | 126 | 51 25 6 | 4 live | 75 | 5.88 | First report of targeted-offspring by Cas9-D10A with an editiing efficiency of 9.1–100% |
Wang et al. [42] | C | Hutchinson-Gilford progeria syndrome | LMNA | gRNA Base editor mRNA | 86 | 41 11 6 | 5 live 1 miscarriage | 83.3 | 12.20 | First report of live edited offspring generated via base-editors; offspring carried a precise C-T conversion in LMNA |